Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study (NCT02129478), a na phase 2 study. The primary outcome is Patient Outcomes.

2. Clinical Question

The registry also names complete CINV control and adverse events as secondary outcomes. However, their outcome results are not reported in the registry record. The study therefore raises two distinct questions: whether the proposed research could be carried out, and whether olanzapine contributes to symptom control. The registry’s primary endpoint addresses the first. Without a comparison group and without posted CINV outcome results, it does not establish the contribution of olanzapine to symptom control.

3. Trial Design

This is a completed phase 2, multicentre feasibility study sponsored by The Hospital for Sick Children. The registry records a single-group model, no masking, and allocation as not applicable. Enrollment was 15. The study started in 2014-03 and reached primary completion in 2016-01.

Participants received olanzapine together with their regular CINV-prevention medications on chemotherapy days. Each child was studied during one chemotherapy cycle. The registry describes recording nausea severity and the times participants vomited or retched on chemotherapy days and for 8 days afterward. It also describes monitoring blood sugar, liver function tests, prolactin, triglycerides, blood pressure, weight, mood and behavior. Reasons for stopping olanzapine early or decreasing the dose were to be recorded.

The design is suited to describing whether study procedures and treatment delivery can be carried out, and to documenting events observed in this group. It does not provide a like-for-like control comparison. In particular, the registry does not describe a group receiving usual medications without olanzapine, or another concurrent treatment group. Differences in CINV over time, if any, could not be separated from chemotherapy, usual medications, participant characteristics, or other influences using a single-group comparison alone.

The primary outcome timeframe is listed as 1 year. The registry’s description says a future study would be considered feasible if enrollment, dose-taking, and tolerability conditions were met. The actual results for those conditions are not reported in the registry record. Details such as the planned statistical analysis, a sample-size justification, interim analyses, and the analysis populations 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

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 Patient Outcomes, measured over 1 year.

The primary endpoint is titled “Patient Outcomes” and is recorded as a count of participants. Its purpose is to assess the feasibility of a future trial examining olanzapine’s contribution to CINV control in pediatric oncology patients. Rather than measuring symptom control as a single treatment-effect estimate, the endpoint defines feasibility using three operational conditions.

The future trial was to be considered feasible if the mean time to enroll 15 patients was 12 months or less per site, if 12 or more patients took at least half of the planned olanzapine doses, and if 3 or less patients experienced significant sedation or dizziness despite dose reduction. These criteria cover recruitment, medication-taking, and a specified tolerability concern. Together, they indicate whether important parts of a larger study might be workable.

A feasibility endpoint is useful because a larger efficacy trial depends on recruitment and treatment procedures being practicable, as well as on acceptable study conduct. Meeting such criteria would not by itself show that olanzapine improves CINV control. Conversely, the registry’s stated feasibility criteria are not equivalent to a direct comparison of symptom outcomes between treatment groups.

The record gives the criteria and a timeframe of 1 year, but does not report the observed values for the criteria or whether the overall feasibility definition was met. It also does not report the primary outcome result in the registry record. The count-type endpoint description alone is therefore insufficient to determine the study’s feasibility conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a count of participants as the primary outcome measure and defines feasibility through criteria concerning enrollment, dose-taking, and tolerability. It does not report the statistical analysis plan, the statistical methods used for the primary endpoint, or the methods used for secondary outcomes. The discussion below distinguishes what the record states from general statistical interpretation.

What does a count endpoint represent?

The endpoint is recorded as a count of participants. In this study, the underlying feasibility definition combines several conditions: enrollment pace, taking at least half of planned doses, and significant sedation or dizziness despite dose reduction. A count can be useful for expressing how many participants meet a criterion, but a count alone does not describe the uncertainty around that finding. To interpret a count, readers also need its relevant denominator, the precise outcome definition, and an analysis method. The registry does not report observed counts for the primary feasibility criteria.

General statistical explanation: for a binary outcome, each participant is classified as meeting or not meeting a specified condition. A proportion expresses the count meeting the condition in relation to the number assessed. A confidence interval is a range of values compatible with the observed data under a statistical model; it conveys uncertainty in an estimate rather than certainty about the true value. No primary feasibility estimate or confidence interval is reported in the registry record, so neither can be interpreted for this endpoint.

What does the single-group design allow?

The study is recorded as single-group, with no masking and allocation listed as not applicable. Participants received olanzapine along with their regular CINV-prevention medications. In a single-group design, outcomes can be described for the participants who were observed, but the design does not directly compare outcomes under olanzapine with outcomes under a concurrent alternative. It therefore cannot isolate the contribution of olanzapine from chemotherapy, other medications, participant characteristics, or changes in symptoms over time.

General statistical explanation: random allocation to concurrent groups can help balance measured and unmeasured characteristics on average, while masking can reduce some forms of influence on outcome assessment or participant reporting. Neither feature is recorded for this study. Their absence does not make descriptive reporting impossible, but it limits the strength of causal comparisons that can be drawn from the results.

How should the feasibility thresholds be understood?

The protocol description sets out three conditions for judging whether a future trial would be feasible: mean enrollment time of 12 months or less per site for 15 patients, 12 or more patients taking at least half of planned olanzapine doses, and 3 or less patients experiencing significant sedation or dizziness despite dose reduction. These are decision criteria specified in the registry description. They are not results. The record does not report the observed mean enrollment time per site, the number meeting the dose criterion, or the number meeting the tolerability condition.

The criteria also address different aspects of feasibility. Recruitment pace is a site-level process measure, while dose-taking and tolerability are participant-level measures. Their denominators, handling of incomplete observations, and method for combining the criteria into an overall conclusion are not reported in the registry record. Without those details and observed results, readers cannot verify whether the overall feasibility rule was satisfied.

What do planning assumptions mean?

A separate planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The illustration is not the trial’s own design: the actual study is single-group. It is therefore not evidence that the study enrolled enough participants to detect an effect, and it should not be interpreted as observed power. The record does not report the planning output values or the sample-size justification for the feasibility study itself.

General statistical explanation: a planning sample size depends on the outcome, the effect considered meaningful, variability, the significance level, and the intended power. Changing the assumed effect changes the planning requirement. An illustration based on a chosen fraction of an observed effect is conditional on that assumption; it does not establish that the assumed effect is clinically meaningful or that the future study will reproduce it. Planning figures are prospective design aids, not findings from participants.

What analysis details are absent?

No analysis entries are listed in the registry. The analysis populations, handling of missing observations, treatment of dose changes, and statistical methods for the primary or secondary outcomes are not reported in the registry record. The record also does not report interim analyses, adjustment for multiple outcome testing, or a sample-size justification. These omissions prevent a detailed assessment of how estimates were generated, which participants contributed to each outcome, or how uncertainty and incomplete data were handled.

General statistical explanation: methods should match the outcome and study design. Binary outcomes are often summarized with counts and proportions, while continuous measurements such as blood tests or weight may require summaries that account for their distribution. Repeated measurements can require methods that account for observations from the same participant being related. The registry describes several measures to monitor, but does not report analysis methods for them. No particular model or test should therefore be inferred.

10. Multiplicity, Missing Data and Analysis Populations

The registry names a primary feasibility endpoint and lists secondary outcomes for complete CINV control and adverse events. It also describes monitoring multiple clinical and laboratory measures, including blood sugar, liver function tests, prolactin, triglycerides, blood pressure, weight, mood, and behavior. The statistical plan for these outcomes and any adjustment for multiple testing are not reported in the registry record.

General statistical explanation: when many outcomes are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory outcomes can help readers interpret a family of tests. The registry identifies primary and secondary outcome categories, but it does not describe a testing hierarchy or multiplicity procedure. No claim about adjusted or unadjusted statistical significance can be made from the posted outcome information.

Missing-data methods are not reported in the registry record. The record does not explain how the analysis would handle a participant who stopped olanzapine early, reduced the dose, missed an assessment, or lacked a complete symptom diary. It states that reasons for early stopping or dose reduction would be recorded, but recording a reason does not itself specify how that participant’s outcome data would be analyzed. The analysis populations, including whether participants would be included according to treatment received or according to enrollment, are also not reported in the registry record.

These gaps matter because feasibility and safety results can depend on who is included and how incomplete follow-up is treated. The registry’s total enrollment of 15 does not show that all participants had complete data for every outcome. The posted record does not provide enough analysis detail to assess the effects of missing observations or outcome multiplicity.

11. 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 0 participants with serious adverse events in the olanzapine group, with 15 participants at risk. It lists 8 participants with other adverse events, also with 15 at risk. These are participant counts in the registry’s safety reporting. They are not a comparison between olanzapine and another treatment, because the study had a single group.

The serious-event count should be read as the number recorded in this study group, not as proof that serious events are impossible or that olanzapine caused no harm. The other adverse-event count is a separate category and should not be treated as a count of serious events. The registry does not report deaths in this adverse-event entry, and no serious adverse-event terms are listed.

The record does not provide event-level descriptions, severity details for the other events, timing, relatedness assessments, or the analysis method used for safety. Those details are not reported in the registry record. Nor does the count indicate whether all participants completed the planned safety monitoring. Without a control group, counts also cannot distinguish events related to olanzapine from events associated with chemotherapy, usual medications, or other circumstances.

General statistical explanation: safety counts in a small study are descriptive. A count of zero can occur even when an event remains possible, and a count of participants with events is not necessarily the same as a count of event episodes. The registry reports participants with events, so the numbers should be interpreted as participant counts rather than as a total number of event occurrences.

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

The study addresses whether a larger pediatric oncology trial of olanzapine might be feasible, using specified recruitment, dose-taking, and tolerability criteria. It enrolled 15 participants and is recorded as completed. The registry describes the intervention, the single-group design, the primary feasibility definition, and safety counts. However, it does not report the observed results for the primary feasibility criteria. Completion of the study therefore cannot be equated with meeting the feasibility definition.

The record also does not report the result for complete CINV control, although that outcome is listed as secondary. The posted information consequently does not provide a numerical estimate of symptom control, a comparison with usual medications alone, or the precision of a treatment-effect estimate. Because there is no concurrent control group, the design could not by itself distinguish the contribution of olanzapine from the effects of chemotherapy, other medications, or other factors.

The adverse-event entries record 0 participants with serious adverse events and 8 with other adverse events among 15 at risk. These figures are descriptive of the study group. They do not establish a comparative safety difference or prove that any event was caused by or unrelated to olanzapine. The registry does not report deaths in the adverse-event entry.

General interpretation: feasibility studies can inform whether procedures and recruitment warrant further evaluation, but they are not automatically designed to establish efficacy. Conclusions should follow the endpoint and design actually used. In this case, the registry record defines feasibility criteria but does not report their results, and it supplies no posted comparative CINV outcome. The available information supports understanding what the investigators intended to assess and what safety counts were recorded, but not a conclusion that the feasibility thresholds were achieved or that olanzapine changed CINV outcomes.

13. Why This Trial Matters Statistically

This trial is statistically important because it separates a question about research feasibility from a question about treatment effect. A future controlled study depends on practical elements such as recruitment, medication-taking, and tolerability. The primary endpoint explicitly focuses on these elements rather than presenting a direct comparative measure of CINV control. Keeping those aims distinct helps prevent a feasibility study from being interpreted as an efficacy trial.

The single-group design also illustrates why design and outcome interpretation must be considered together. Counts observed among participants can describe what happened in the study group, but without a concurrent comparator they do not isolate the contribution of olanzapine. This is particularly relevant in a setting where participants also received regular medications to prevent CINV and were undergoing chemotherapy.

The endpoint definition is concrete: it sets criteria for enrollment pace, dose-taking, and a specified tolerability concern. That clarity can support planning, but the registry does not report the observed values needed to judge whether the criteria were met. Prespecified criteria are not a substitute for reported results. The record’s missing outcome results therefore limit what can be learned about the study’s main feasibility question.

General statistical lesson: a result is most informative when the design, outcome definition, analysis method, denominator, and uncertainty are all clear. Counts of adverse events and an enrollment total have a useful descriptive role, but cannot answer every question about treatment effects, rare events, or generalizability. This record offers an example of why readers should distinguish a study’s stated purpose, its available results, and the conclusions those results can support.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations arise from the design and the registry information. The study had a single group, no masking, and no randomized allocation. It therefore lacks a concurrent control comparison and cannot isolate olanzapine’s contribution to CINV outcomes. Participants received usual CINV-prevention medications alongside olanzapine, further defining the results as observations within a combined treatment context.

Enrollment was 15, and each child was studied during one chemotherapy cycle. The study’s observations consequently concern a limited group and a limited treatment period. The registry does not report participant characteristics beyond the age range described in the study summary, nor does it report the distribution of chemotherapy regimens or other factors that could help readers judge how broadly the observations apply. Such details are not reported in the registry record.

The main limitation for interpreting the primary endpoint is that the registry gives the feasibility criteria but not their observed results. It therefore does not report whether the enrollment, dose-taking, and tolerability thresholds were met. The secondary outcome of complete CINV control is named, but its result is not reported in the registry record. No numerical symptom-control estimate or measure of precision is available in the posted results.

Safety interpretation is also constrained. The record lists participant counts for serious and other adverse events, but does not report event descriptions, timing, relatedness, or detailed follow-up. Deaths are not reported in the adverse-event entry. Missing-data procedures, analysis populations, statistical methods, and a sample-size justification are not reported in the registry record. These gaps limit assessment of completeness, uncertainty, and analytic choices.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study — NCT02129478.
• Registry record last updated 2020-04-07; status last verified 2020-03.
• Results first posted 2020-04-07.
• 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.

18. Record Summary

The registry describes a completed phase 2, multicentre, single-group feasibility study of olanzapine for prevention of CINV in children receiving chemotherapy. It records no masking, enrollment of 15, and a study period from 2014-03 to primary completion in 2016-01. Participants received olanzapine with their regular CINV-prevention medications during one chemotherapy cycle.

The primary endpoint defined future-trial feasibility using enrollment pace, dose-taking, and tolerability criteria. The registry does not report the observed primary endpoint results or whether the criteria were met. Complete CINV control is listed as a secondary outcome, but its result is not reported in the registry record.

The adverse-event entries list 0 participants with serious adverse events and 8 with other adverse events among 15 at risk. The single-group design does not support a controlled estimate of olanzapine’s contribution to CINV control or comparative safety. Analysis methods, missing-data handling, and analysis populations are not reported in the registry record.