Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting (NCT02484911), a randomized phase 3 study. The primary outcome is Proportion of Participants Receiving HEC With Complete Response in Overall Phase.

2. Clinical Question

3. Trial Design

The registry describes NCT02484911 as a randomized, single-center phase III trial with a parallel-group design and no masking. The sponsor was First Affiliated Hospital of Harbin Medical University. Enrollment was 120. The study began in 2015-05, primary completion was 2016-09, and its status is completed.

Participants were assigned to an olanzapine regimen or a control regimen. Both regimens included aprepitant, palonosetron, and dexamethasone; olanzapine was included only in the intervention regimen. The record does not report the allocation procedure beyond randomized assignment, nor does it report whether allocation concealment was used.

The registry identifies the primary outcome as the number of participants receiving HEC with complete response in the overall phase. The timeframe was 0 to 120 hours. The efficacy population was the full analysis set, defined as patients who received HEC, took a dose of study drug, and completed treatment. Primary endpoint counts were 20 of 20 in the olanzapine regimen and 15 of 17 in the control regimen. These analyzed counts describe the HEC primary endpoint population, not necessarily all 120 enrolled participants.

The record also lists outcomes for acute and delayed phases, no vomiting, and MEC. It does not report the number randomized to each regimen, the reasons for exclusions from the primary analysis, or the handling of missing endpoint observations. Further details of the randomization method and the trial’s sample-size justification 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.

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 Proportion of Participants Receiving HEC With Complete Response in Overall Phase, measured over 0 to 120 hours.

The primary endpoint was the proportion of participants receiving HEC who achieved complete response during the overall phase, defined as 0 to 120 hours after chemotherapy began. The registry defined complete response as no vomiting with no rescue therapy. Thus, the outcome combines the absence of vomiting with the absence of rescue treatment; it is not a measure of vomiting alone.

The posted primary counts were 20 participants in the olanzapine regimen and 15 in the control regimen, with analyzed group sizes of 20 and 17, respectively. This is a binary endpoint: each participant either met the complete-response definition or did not. Counts and proportions make the outcome clinically interpretable, while a between-group risk difference describes the contrast in the observed proportions.

In general, an overall-period endpoint captures whether the defined response was maintained throughout a specified interval, rather than only during an early or later subperiod. This endpoint is used to represent response across the full 0 to 120 hour timeframe. It does not, on its own, describe symptom severity, duration of individual episodes, quality of life, or the experience of participants outside the defined HEC full analysis set. Those measures are not reported as the primary endpoint in the registry record.

7. Results Posted in the Registry

• Olanzapine Regimen: 100.0% (20/20) versus 88.2% (15/17) on control; risk difference 11.8 percentage points (95% CI -3.6 to 27.1), risk ratio 1.13 (0.95–1.35); unadjusted two-proportion z-test p = 0.115.

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.

Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Aprepitant Regimen: 88.2% (15/17) versus 100.0% (20/20) on control; risk difference -11.8 percentage points (95% CI -27.1 to 3.6), risk ratio 0.88 (0.74–1.05); unadjusted two-proportion z-test p = 0.115.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aprepitant Regimen and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Olanzapine Regimen: 85.0% (17/20) versus 35.3% (6/17) on control; risk difference 49.7 percentage points (95% CI 22.1 to 77.3), risk ratio 2.41 (1.23–4.70); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Olanzapine Regimen than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Olanzapine Regimen: 90.0% (18/20) versus 88.2% (15/17) on control; risk difference 1.8 percentage points (95% CI -18.4 to 21.9), risk ratio 1.02 (0.81–1.28); unadjusted two-proportion z-test p = 0.863.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Olanzapine Regimen and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover complete response and no vomiting in different chemotherapy groups and time periods. The overall pattern is not uniform across those definitions and intervals. For HEC, the posted no-vomiting counts show a stronger observed separation over the overall period than in the acute phase. Complete response in the delayed phase has the same group counts as the primary endpoint, while the secondary list also includes HEC complete response in the acute phase and outcomes for MEC.

These endpoints are related to the primary question, but they are not interchangeable. No vomiting does not require that rescue therapy was absent, whereas complete response does. Acute, delayed, and overall periods also describe different time windows. Accordingly, a secondary result with a different pattern does not directly contradict the primary endpoint; it addresses a different outcome definition or period.

Several secondary analyses have small group counts, and their statistical results differ from the primary comparison. The registry reports p values for the listed analyses, while the recalculations are unadjusted comparisons of the posted counts. The record does not describe a prespecified hierarchy, multiplicity correction, or other strategy for interpreting the family of outcomes. When many outcomes are examined, isolated small unadjusted p values have a greater chance of arising by chance. This general concern means that secondary findings should carry less confirmatory weight than the primary endpoint, particularly when no adjustment plan is reported.

The secondary outcomes can help describe the consistency of observed patterns across definitions and timeframes, but they cannot resolve the primary endpoint’s uncertainty. The registry’s incomplete detail on missing data and analysis procedures further limits comparisons across outcome populations. These findings are best treated as contextual evidence that may motivate further study, rather than as independent confirmation of a single overall conclusion.

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

• Proportion of Participants Receiving HEC With Complete Response in the Acute Phase
• Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase
• Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase
• Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase
• Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase
• Proportion of Participants Receiving MEC With Complete Response in the Acute Phase
• Proportion of Participants Receiving MEC With Complete Response in the Delayed Phase
• Proportion of Participants Receiving MEC With No Vomiting in the Overall Phase

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: each participant either achieved complete response during the overall phase or did not. For a binary outcome, the observed proportion is the number meeting the endpoint divided by the number analyzed in that group. The registry gives counts and analyzed denominators, allowing a simple unadjusted comparison of those proportions.

What the risk difference expresses

In general, a risk difference subtracts one group’s event proportion from the other’s. It expresses the absolute contrast on the proportion scale. A positive estimate under the stated comparison direction means the event proportion is higher in the intervention group; a negative estimate means it is lower. The primary recalculation reports a risk difference and confidence interval, but the interval crosses zero. Because complete response is the event, interpretation must keep the endpoint definition in view: the event requires both no vomiting and no rescue therapy.

How to read a confidence interval

In general, a confidence interval is a range of effect estimates compatible with the observed data under the method used. It conveys uncertainty about the estimated contrast, not a range containing a fixed proportion of individual participant outcomes. An interval spanning zero for a risk difference includes the possibility of no group difference under that method. The interval’s width is also important: a wide interval allows a broad range of plausible contrasts and reflects limited precision. The registry does not specify the confidence level for the recalculated interval.

How to read p values

In general, a p value measures how unusual data at least as discrepant as those observed would be under a specified null model and analysis procedure. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an observed difference. The primary recalculation gives p = 0.115, while the registry reports p = 0.397 from a Chi-squared analysis. These values come from different presentations of the comparison; the detailed sponsor analysis is not fully described in the record. A p value should be considered alongside the endpoint counts, effect estimate, and interval, rather than used as a standalone verdict.

Why the test and analysis details matter

In general, tests for binary outcomes can differ in how they handle small groups, continuity corrections, stratification, covariate adjustment, or the precise analysis population. The registry names Chi-squared for its reported analysis but does not describe additional details of the test or model. It is therefore not possible to attribute the difference between the posted p values to a particular analytic choice. No adjustment variables or stratification factors are reported for the primary analysis.

Planning illustrations are not observed power

The sample-size illustrations use an effect based on the observed effect and consider planning for 100%, 75%, and 50% of that observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations give participants per arm for 80% power and participants per arm for 90% power. For the overall-phase no-vomiting comparison, the entries are 14 and 19 for planning at 100% of the observed effect; 27 and 36 for planning at 75%; and 63 and 83 for planning at 50%. These are hypothetical planning quantities, not the trial’s enrollment targets, and not evidence of the probability that this completed study detected an effect. The trial’s own sample-size justification is not reported in the registry record.

In general, planning from an observed effect is sensitive to that estimate. If an observed contrast is unusually large or small, planning directly from it can produce an illustration that does not reflect the effect a future study should expect. The smaller-effect scenarios make that sensitivity visible, but they do not establish which effect size is appropriate for a future trial.

Multiplicity and endpoint families

The registry lists 12 outcome measures and 10 posted secondary outcomes. It also lists 10 analyses. When many outcomes are tested, the chance of obtaining one or more small p values by chance can increase. In general, multiplicity procedures control or account for this issue through a prespecified testing strategy. Such a strategy, including any adjustment or hierarchy, is not reported in the registry record. The secondary p values should therefore be read as unadjusted evidence, with less confirmatory weight than a result from a clearly specified multiplicity-controlled plan.

Finally, the endpoint population is defined by receipt of HEC, taking study drug, and completing treatment. This definition is part of the registry’s full analysis set description, but it does not explain how missing outcome data or early discontinuation were handled. Those details are not reported in the registry record. The interpretation consequently depends on the posted counts and the stated analysis population, without assumptions about unreported procedures.

11. Confidence Intervals and Precision

The primary endpoint counts are 20 of 20 for the olanzapine regimen and 15 of 17 for the control regimen. The recalculated risk-difference interval crosses zero. This means the posted data are compatible with no difference under the calculation, as well as with contrasts in either direction. The registry does not provide a confidence level for that recalculated interval, so a particular confidence percentage should not be assigned to it.

Precision concerns how narrowly the data constrain the estimated contrast. In general, smaller analyzed groups tend to provide less information about a binary outcome, especially when most participants in a group have the event. Here, the primary endpoint has relatively few analyzed participants and complete response was observed in every participant in one group. Those features limit what can be learned about the range of plausible group differences from these counts alone.

The recalculated unadjusted p value is 0.115, while the registry reports a Chi-squared p value of 0.397. The registry does not report enough detail to explain the difference. Neither value substitutes for the interval: a p value summarizes compatibility with a null model under an analysis, whereas the interval describes the range of estimates supported by that calculation. The primary endpoint’s interval crossing zero is a direct indication that the estimate is not precise enough to exclude no difference by that interval criterion.

Secondary comparisons also vary in the amount of separation and uncertainty. Their estimates come from the posted group counts, and the registry’s secondary analysis details are limited. Any interval or p value should be interpreted in the context of the endpoint definition, analysis population, and multiple outcomes examined. In general, wider uncertainty and unadjusted testing call for caution rather than a definitive reading of an individual secondary result.

12. Analyses Reported by the Sponsor

The registry reports a Chi-squared analysis for the primary comparison with p = 0.397. A simple unadjusted recalculation from the posted counts gives p = 0.115 and a risk-difference interval that crosses zero. These are distinct inferential results. The record does not report enough information about the sponsor’s analysis to establish whether differences in test implementation, analysis population, or another factor account for the gap.

For the overall-phase no-vomiting secondary outcome, the registry reports p = 0.02, while the unadjusted recalculation gives p = 0.002. For the acute-phase no-vomiting outcome, the registry reports p = 1.0, while the unadjusted recalculation gives p = 0.863. These examples likewise show that the sponsor-reported and simple recalculated p values are not interchangeable.

The recalculations are simple, unadjusted analyses based on the posted summary counts. They do not reconstruct a fuller sponsor analysis that is not described in the record. The sponsor’s reported results should therefore be identified as the registry’s own analysis, while recalculated values are useful as transparent comparisons from the posted counts. The analysis methods and populations underlying the reported tests are not fully described in the registry record.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 10 posted secondary outcomes. Ten analyses are listed. The primary endpoint is identifiable, but the record does not report whether secondary outcomes were arranged in a testing hierarchy, whether any p-value adjustment was planned, or whether the analyses were intended to be confirmatory or exploratory. A multiplicity plan is therefore not reported in the registry record.

In general, testing several outcomes can increase the chance that at least one result appears statistically notable even when no corresponding effect exists. Adjustment methods can address that issue, but may change how individual p values are interpreted. Without a reported strategy, the secondary p values should be treated as unadjusted and considered in light of the number and variety of outcomes. This does not make the outcomes irrelevant; it limits the strength of confirmatory claims based on any one result.

The full analysis set for efficacy includes patients who received HEC, took a dose of study drug, and completed treatment. The record does not report how many enrolled participants were excluded from the primary endpoint population, the reasons for exclusion, or how missing observations were handled. It also does not report whether participants with incomplete follow-up were counted as nonresponders, omitted, or addressed by another method.

The registry describes the primary efficacy population, but does not provide enough information to judge the effect of missing data or treatment discontinuation on the results. The sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record. These gaps matter because analysis-population choices and missing-data procedures can affect the estimated proportions and their uncertainty. No assumptions about those unreported decisions should be made when interpreting the posted counts.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event record gives safety counts for 56 participants in the olanzapine regimen and 58 in the control regimen. Serious adverse events related to treatment are recorded for zero participants in each group. Deaths are also recorded as zero in both groups. Other adverse events are recorded for 21 participants in the olanzapine regimen and 14 in the control regimen.

These are counts, not rates adjusted for exposure time, and the registry does not provide event-level detail or a list of top serious adverse-event terms. A count of zero for serious events or deaths means none were recorded in the stated group counts; it does not establish that an event is impossible or rule out uncommon harms. The record also does not report the severity, duration, or individual nature of the other adverse events in this summary.

The safety group sizes differ from the primary efficacy group sizes. The record does not explain the distinction between the safety and efficacy populations. These safety figures should therefore be read as the registry’s reported counts, not combined with the efficacy findings or used to infer a comparative safety profile beyond what is recorded.

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

The primary endpoint records complete response during 0 to 120 hours after chemotherapy initiation, using a definition that requires no vomiting and no rescue therapy. In the HEC full analysis set, the posted counts are 20 of 20 for the olanzapine regimen and 15 of 17 for the control regimen. The unadjusted recalculation gives p = 0.115, and its risk-difference interval crosses zero. The registry’s own Chi-squared analysis reports p = 0.397.

These results describe the participants included in the stated analysis population. They do not establish that the regimens would produce the same observed results in a different population, center, chemotherapy setting, or study design. Although the trial enrolled 120 participants overall, the primary endpoint counts cover only the listed HEC analysis groups. The registry does not report enough information to reconcile the overall enrollment with these endpoint-specific counts.

A p value is not a measure of treatment importance, and an observed difference in counts is not by itself proof of a reproducible effect. The uncertainty around the recalculated contrast is substantial enough to include no difference. The sponsor-reported analysis and the simple recalculation also yield different p values, and the registry does not describe enough analytic detail to explain why.

The secondary outcomes provide additional descriptions of vomiting and complete response across periods and chemotherapy groups. They do not erase uncertainty in the primary result. Because the record does not report a multiplicity plan, isolated unadjusted secondary findings should not be treated as definitive confirmation. Likewise, the safety counts do not fully characterize adverse-event type or severity.

In short, the registry documents observed endpoint and safety counts, together with reported and recalculated statistical results. It does not support a broader claim about outcomes beyond the measured endpoints and listed analysis populations, nor does it provide all details needed to assess missing observations, analysis choices, or the certainty of secondary findings.

16. Why This Trial Matters Statistically

This trial illustrates why a clinical comparison should be read through its endpoint definition, denominator, and analysis method, rather than through a single p value. Complete response combines two conditions: no vomiting and no rescue therapy. The separate no-vomiting outcomes therefore answer related but different questions, and their results need not match the complete-response result.

The primary endpoint is based on relatively small analysis groups, and the intervention group has no observed failures under the recorded complete-response definition. Such data can produce an apparently clear difference in counts while still leaving substantial uncertainty about the underlying contrast. The recalculated interval crossing zero makes that uncertainty visible. It is a reminder that an observed group pattern and a precise estimate are not the same thing.

The registry’s reported Chi-squared p value differs from the simple unadjusted recalculation. This makes transparent reporting of the analysis method, analysis population, and any adjustments especially important. Without those details, readers cannot determine the reason for the difference or reproduce the sponsor’s analysis from the registry record.

The secondary outcomes also demonstrate the challenge of interpreting multiple endpoints. Different periods and outcome definitions produce different patterns, and the record does not describe how multiplicity was handled. In general, that uncertainty lowers the weight of isolated secondary p values. Finally, planning illustrations derived from an observed effect are not a substitute for a prospective sample-size justification. The registry’s own justification is not reported. These issues make the trial a useful example of how outcome construction, precision, analysis transparency, and multiplicity shape interpretation.

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.

This record leaves important design and analysis details unreported. It identifies randomization and a parallel-group structure but does not describe the sequence-generation method, allocation concealment, or any stratification. Masking was none. The registry does not report whether that design feature was considered in the outcome assessment or analysis.

The primary endpoint population is the full analysis set of patients who received HEC, took a dose of study drug, and completed treatment. The record does not state how many participants were randomized to each arm, how many did not meet the efficacy criteria, or why. It also does not report a missing-data strategy, the handling of early discontinuation, or whether sensitivity analyses were performed.

The primary endpoint group counts are much smaller than the total enrollment, but the record does not provide enough information to explain the relationship. Safety counts use different group sizes from the primary efficacy outcome, and the record does not describe the populations in enough detail to account for this difference. No generalization to all enrolled participants should be assumed from the endpoint counts alone.

The reported primary Chi-squared p value differs from the unadjusted recalculation. Additional details needed to reproduce the sponsor’s analysis are not reported in the registry record. The record also does not report the confidence level for the recalculated interval, a sample-size justification, interim analyses, or a multiplicity plan. Multiple outcomes are listed, but the strategy for interpreting them is not stated.

Finally, the safety summary provides counts without detailed event descriptions, severity, or exposure-adjusted information. The absence of recorded serious events or deaths in these groups cannot establish the absence of uncommon events. These limitations do not invalidate the posted counts, but they constrain the precision and scope of conclusions that can be drawn from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting — NCT02484911.
• Registry record last updated 2017-03-30; status last verified 2016-06.
• Results first posted 2017-03-30.
• 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

NCT02484911 is a completed randomized, single-center phase III trial with a parallel-group design and no masking. It enrolled 120 participants. The olanzapine regimen added olanzapine to aprepitant, palonosetron, and dexamethasone; the control regimen used aprepitant, palonosetron, and dexamethasone.

The primary HEC endpoint was complete response from 0 to 120 hours, defined as no vomiting and no rescue therapy. Counts were 20 of 20 in the olanzapine regimen and 15 of 17 in the control regimen. The recalculated unadjusted p value is 0.115, while the registry reports a Chi-squared p value of 0.397. The recalculated risk-difference interval crosses zero.

Secondary outcomes address other periods, no vomiting, and MEC. The registry does not report a multiplicity plan, missing-data procedures, the sample-size justification, or enough detail to reproduce the sponsor’s analysis. Safety counts record zero related serious adverse events and zero deaths in both groups.