Auricular Neurostimulation for Cyclic Vomiting Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Auricular Neurostimulation for Cyclic Vomiting Syndrome (NCT03434652), a randomized na study. The primary outcome is Rhodes Index of Nausea, Vomiting & Retching (INVR).

2. Clinical Question

3. Trial Design

The registry describes a randomized, quadruple-masked, crossover pilot study sponsored by the Medical College of Wisconsin. The study began on 2018-01-31, reached primary completion on 2021-03-03, and is listed as completed. The recorded enrollment is 47. The study title and summary describe auricular neurostimulation for children and adults with cyclic vomiting syndrome.

The acute treatment plan compared active percutaneous neurostimulation with sham treatment. A participant was to be randomized to active or sham treatment for 5 days during the first illness cycle, then cross over to the other treatment during the second illness cycle. This within-participant arrangement can allow a participant's outcomes under the two treatments to be compared, but interpretation depends on how the sequence, illness cycles, and repeated measurements are handled. The registry record does not report a statistical plan for those issues.

The record separately describes chronic treatment as 6 consecutive weeks of active, open-label neurostimulation. Daily symptom scores were to be averaged by week and compared between baseline and week 6. Because this treatment is described as open-label and no concurrent comparator is specified for the chronic arm, its design differs from the blinded acute crossover comparison.

The record states that the acute treatment design was subsequently deemed unfeasible and that the trial was terminated early for that arm. It does not explain the operational reasons in further detail or state how this affected enrollment, follow-up, or the planned analyses. The registry record also does not report a detailed allocation sequence, the masking procedures, or a statistical analysis plan. Those details should not be inferred from the design labels alone.

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: Study design for Acute treatment arm was subsequently deemed unfeasible and the trial terminated early for the Acute treatment arm.

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.

Population: Acute therapy; 15 subjects enrolled; 4 dropped out and 1 ineligible for total of n=10 completed trial Chronic therapy: 32 subjects enrolled; 1 dropped out and 1 ineligible for total of n=30 completed trial

6. Primary Endpoint

The registry lists the primary outcome as Rhodes Index of Nausea, Vomiting & Retching (INVR), measured over Acute arm: at the start of the first and second illness cycle through next 7 days for each illness cycle (active and sham therapy). Chronic arm: from date of baseline assessment (therapy start date) through 6 weeks of therapy..

The primary endpoint was the Rhodes Index of Nausea, Vomiting and Retching, a validated scale recorded as a score on a scale. The registry describes a 0-32 range, with 0 indicating no symptoms and 32 indicating the worst possible nausea and vomiting. Higher scores indicate worse symptoms. The measure therefore represents symptom severity rather than a count of illness episodes or a time-to-event outcome.

For the acute arm, daily scores were to be assessed from the start of each illness cycle through the next 7 days. The description says baseline day 1 and end-of-therapy day 7 scores were compared for active and sham treatment. For the chronic arm, daily scores were to be averaged for each week of treatment, with baseline assessment compared with week 6.

General: a repeated symptom scale can characterize changes in symptom burden over a treatment period and gives a defined direction for interpreting scores. Here, a lower score represents less reported nausea and vomiting severity. However, the registry record does not provide the observed scores, changes, variability, or a treatment-effect estimate. The endpoint definition alone cannot establish the size or precision of any difference between treatment conditions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as a continuous score summarized by a mean and standard deviation. It does not report the numerical results or the statistical methods used to analyze them. The concepts below explain how such methods are generally interpreted; they do not describe a confirmed analysis plan for this study.

What does a mean score describe?

General: the mean is an average score for the participants included in an analysis. For this endpoint, higher values correspond to worse nausea and vomiting severity. A mean can provide a concise description of a group's symptom scores, but it does not show how scores are distributed among participants. Two groups can have similar means while differing in their spread or in the pattern of individual responses.

The standard deviation describes how dispersed individual scores are around their group mean. A larger standard deviation indicates greater variability in scores within that group. It is not the same as the uncertainty in the estimated mean or in a treatment contrast. The registry record does not report means or standard deviations for the primary endpoint, so these features cannot be assessed from its outcome results.

How would a treatment contrast be interpreted?

General: an analysis could express a difference between mean scores under active and sham treatment, with the direction interpreted using the scale's scoring rule. A negative active-minus-sham contrast would indicate lower average scores under active treatment, whereas a positive contrast would indicate higher scores under active treatment. This describes the meaning of a possible contrast, not a result from this study. No such contrast is reported in the registry record.

A confidence interval around an estimate conveys statistical uncertainty. A narrow interval indicates greater precision than a wide interval, subject to the analysis assumptions. If an interval includes values consistent with effects in more than one direction, the evidence may not clearly distinguish those possibilities. The registry record does not report a confidence interval or other precision measure for the primary endpoint. It also does not report a primary-outcome p-value.

What matters in a crossover design?

General: in a crossover study, participants receive more than one treatment condition, and their outcomes may be compared within participant. This can account for stable differences between people, but it does not automatically resolve changes over time, differences between treatment periods, or possible carryover from an earlier treatment. The order of treatments and the timing of measurements can also matter. The acute plan specified active or sham treatment in the first illness cycle followed by the other treatment in the second cycle. The statistical handling of sequence, period, and carryover is not reported in the registry record.

The acute outcome description refers to daily observations and comparisons between day 1 and day 7. Repeated measurements from a participant are related rather than independent. General: an analysis of repeated scores should account for that dependence or define a suitable participant-level summary. Treating related daily observations as if they were unrelated can misrepresent uncertainty. The registry record does not state how daily observations were used in an analysis.

How does the chronic measurement schedule differ?

The chronic arm describes active open-label treatment for 6 consecutive weeks, with daily scores averaged within each week and a comparison between baseline and week 6. General: reducing repeated daily scores to weekly averages can create a simpler summary, while potentially obscuring day-to-day variation. A baseline-to-follow-up comparison describes change over time, but without a concurrent comparator it does not isolate the change attributable to treatment. The registry record does not report a chronic-arm estimate or a method for analyzing the repeated weekly measures.

What can planning calculations establish?

General: a sample-size calculation uses assumptions about the effect to detect, variability, allocation, and a chosen statistical error rate. The registry's stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and fractions of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a treatment effect occurred. The record does not report the primary outcome results needed to evaluate an observed effect in this statistical interpretation.

Over-dispersion is a general concern when count outcomes vary more widely than a model assumes; it can make uncertainty estimates too optimistic if ignored. The primary endpoint is described as a continuous symptom score, not a count outcome. The registry record does not report a model, an over-dispersion assessment, or any other fitted statistical procedure. No specific modeling choices should therefore be attributed to the study.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described across several treatment conditions and time points: acute active and sham treatment with day 1 and day 7 scores, and chronic treatment with baseline and week 6 measurements. The registry record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report a single primary contrast, a hierarchy among comparisons, or a multiplicity adjustment.

The record lists secondary outcomes including Numeric Pain Scale, Anxiety, Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life, Functional Disability Inventory- Disability in Children, Disability in Adults, and Symptom Response Scale. It records 7 outcome measures and 0 analyses. No numerical results or analysis descriptions for these secondary outcomes are reported. General: testing several outcomes or time points can increase the chance of obtaining an apparently unusual result by chance if each is considered separately. Prespecified priorities and adjustment procedures can help readers understand how that issue was addressed, but they are not reported in the registry record.

The registry record does not report how missing outcome measurements were handled, whether imputation was used, or how incomplete follow-up affected analysis. It also does not describe the analysis population, such as whether analyses followed randomized assignment or included only participants with particular follow-up data. The enrollment figure alone cannot identify the number contributing to each outcome analysis.

The early termination of the acute arm for feasibility makes the reporting of available observations and analysis populations especially relevant. The record does not provide those details. Consequently, the effects of missingness, selection into analyses, or multiplicity on the interpretation cannot be assessed from the registry record.

11. 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 registry lists serious adverse events, other adverse events, and deaths separately for the acute active, acute sham, and chronic treatment groups. It records zero serious adverse events in all three groups and zero deaths in all three groups. For other adverse events, it records zero in the acute active group, zero in the acute sham group, and 7 in the chronic group. These are event counts as entered in the record.

The entries also give the number at risk for each category: 10 for each acute group and 30 for the chronic group. These group figures should be read as reported, without combining groups or converting them into percentages. The registry record does not give descriptions of the 7 other adverse events, their timing, severity, or relationship to treatment. It also does not report a statistical comparison of safety outcomes.

General: a zero count in a registry entry means that no event of that listed type was recorded for that group in the reported data. It does not prove that an event is impossible or establish that two treatments have identical safety profiles. The chronic arm was open-label active treatment, whereas the acute groups represent active and sham treatment. Differences in treatment structure and available follow-up limit direct interpretation of the counts as a comparative safety analysis.

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

The record is useful for understanding the study's intended question, the treatment schedules, and the primary symptom measure. It documents a randomized, quadruple-masked crossover plan for acute active-versus-sham treatment and a separate open-label chronic treatment plan. It also makes clear that the acute arm was deemed unfeasible and terminated early.

What the record does not provide is an analyzed primary outcome contrast, its uncertainty, or a numerical summary of symptom scores. There is therefore no registry-based estimate of how active treatment compared with sham treatment in the acute design, or how chronic-arm scores changed from baseline to week 6. The outcome definitions describe what was intended to be measured; they are not outcome findings.

Likewise, the recorded adverse-event counts do not establish comparative safety. The serious event and death entries are zero in each listed group, and other adverse events are recorded in the chronic group. Without event descriptions, comparative analyses, or additional follow-up information, those counts have limited interpretive scope.

General: a trial design can show how investigators planned to reduce bias, and a defined endpoint can make the intended measurement clear. Neither alone establishes a treatment effect. To assess an effect, readers need analyzed results, information about who contributed data, a stated analysis approach, and an account of uncertainty. Those elements are not reported for the primary outcome in the registry record. Accordingly, the posted information supports a description of the study and its reporting gaps, not a claim that neurostimulation does or does not improve symptoms.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combined two different treatment questions within a pilot study: an acute active-versus-sham crossover plan and a chronic open-label treatment period. These designs require different interpretations. A crossover comparison can use within-participant information, while an open-label baseline-to-follow-up comparison does not provide the same concurrent control. Keeping those questions distinct is important when reading the endpoint schedule.

The primary measure is a repeated symptom score with an explicit direction: higher scores indicate worse nausea and vomiting. That direction helps explain what a possible score contrast would mean. The measurement schedule also illustrates why the definition of an endpoint is not always a single number: the acute and chronic arms have different time points and summaries. The registry states that the primary outcome has several categories or time points and was not reduced to one comparison.

The acute arm's early termination for feasibility underscores that intended design and completed analysis are not interchangeable. The registry record reports no primary outcome analyses, so the planned comparison cannot be evaluated from the posted results. This distinction is important in biostatistics: study registration can document aims and methods, but inference depends on the data summaries and analysis details that are reported.

The record also illustrates the limits of interpreting adverse-event counts without event descriptions or comparative analyses. Overall, the study is informative as a case in endpoint definition, crossover planning, repeated measurements, and incomplete registry reporting. It does not provide the numerical evidence needed to estimate a primary treatment effect.

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.

The main trial-specific limitation in interpreting the registry record is that it reports no primary outcome analyses. It defines the Rhodes Index measurement schedule but does not report observed scores, mean changes, variability, a treatment contrast, or an uncertainty interval. The direction and magnitude of any treatment effect therefore remain unavailable in the posted results.

The acute arm was terminated early after its design was deemed unfeasible. The record does not explain the reason in detail, state how many participants contributed acute outcome data, or describe whether the planned crossover sequence was completed. It also does not report an analysis addressing possible period or carryover effects in the acute design.

The acute and chronic arms differ in treatment structure and outcome timing. Acute treatment was planned as active versus sham across illness cycles; chronic treatment was active and open-label for 6 consecutive weeks. The registry record does not provide a concurrent chronic comparator or an analysis that would separate change over time from treatment-associated change.

Missing-data procedures and analysis populations are not reported. The record also does not provide a statistical analysis plan, a prespecified primary contrast, or a multiplicity procedure for the several outcomes and time points. These omissions prevent assessment of how incomplete observations, analytic choices, or multiple comparisons may affect interpretation.

Safety entries give event counts but not descriptions of the other adverse events, timing, severity, or treatment attribution. They are not accompanied by comparative statistical analyses. These limitations concern what can be concluded from the registry record; they do not establish that unreported analyses or information do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Auricular Neurostimulation for Cyclic Vomiting Syndrome — NCT03434652.
• Registry record last updated 2026-02-13; status last verified 2026-01.
• Results first posted 2026-02-13.
• 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

NCT03434652 is a completed randomized, quadruple-masked crossover pilot study sponsored by the Medical College of Wisconsin. It enrolled 47 participants and studied percutaneous auricular neurostimulation for children and adults with cyclic vomiting syndrome. The registry describes an acute active-versus-sham crossover plan and a separate 6-week open-label chronic treatment arm.

The primary endpoint was the Rhodes Index of Nausea, Vomiting and Retching, scored from 0-32, with higher scores indicating worse symptoms. The acute design was deemed unfeasible and terminated early. The registry records 0 analyses and does not report numerical primary outcome results, analysis methods, or missing-data procedures.

Serious adverse events and deaths are recorded as zero in each listed group. Other adverse events are recorded as zero in each acute group and 7 in the chronic group. The record does not provide further descriptions or comparative safety analyses. The posted information documents the planned question and selected safety counts but does not support an estimate of the primary treatment effect.