Fade Upon TOF Stimulation Induced by Succinylcholine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fade Upon TOF Stimulation Induced by Succinylcholine (NCT02425449), a randomized phase 4 study. The primary outcome is Fade on Train of Four Stimulation.

2. Clinical Question

The clinical measurement captures the relative force of the fourth contraction compared with the first. The registry description states that this ratio is normally one before succinylcholine, and that a ratio below one after administration reflects greater diminution of the fourth contraction than the first. The reported endpoint is therefore intended to characterize the most pronounced recorded fade during the effect of succinylcholine, rather than an average across all recorded stimulation times.

The registry record does not report a separate hypothesis test for dose differences, onset versus offset, or the existence of fade. It reports arm-level endpoint summaries, but does not identify the dose corresponding to each reported arm label. This limits what can be concluded about how the measured response varied across the dose descriptions.

3. Trial Design

The registry describes a randomized, parallel-group, unmasked phase 4 study sponsored by University of Toledo Health Science Campus. Its status is completed. The listed enrollment is 19. The study start is recorded as 2015-04, and primary completion is recorded as 2017-01-04. Additional information about recruitment, sites, eligibility criteria, and participant characteristics is not reported in the registry record.

The intervention descriptions list five succinylcholine dose levels: 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg, 0.25 mg/kg, and 0.3 mg/kg. However, the posted results label the outcome groups Arm 1 through Arm 5, and the registry record does not make the dose-to-arm mapping clear in those result labels. Arm 1 is identified as the control, but its outcome entry has a participant count of 0 and no mean or standard deviation. The other reported rows are Arm 2, with n=4, Arm 3, with n=5, Arm 4, with n=5, and Arm 5, with n=5.

The measurement procedure was repeated ulnar nerve stimulation at the wrist, with four stimulations over 1.5 seconds every 20 seconds. The ratio of the fourth contraction to the first was measured before and after succinylcholine administration, and the lowest post-administration ratio was the primary outcome. The expected duration named for the measurement timeframe is 6-10 minutes, described as the duration of the effect generally expected for succinylcholine.

The registry record does not report allocation concealment, the randomization sequence method, treatment administration details beyond the arm descriptions, or whether outcome measurement was performed by masked assessors. It also does not report a protocol or a detailed statistical analysis plan. The unmasked designation describes the study’s registered masking status; it does not by itself establish how any specific measurement or analysis was conducted.

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 Fade on Train of Four Stimulation, measured over for the duration of the effect of succinylcholine generally expected to be 6-10 minutes.

The primary endpoint is the lowest recorded ratio of the fourth contraction to the first contraction (T4 to T1) after succinylcholine administration. The ulnar nerve was stimulated at the wrist four times over 1.5 seconds every 20 seconds, and contraction force was measured. The registry describes a pre-administration ratio normally equal to one. A post-administration ratio below one indicates that the fourth contraction diminished more than the first.

Using the lowest recorded ratio focuses on the most pronounced measured fade during the observation period. It does not summarize the full time course, nor does it describe how quickly the ratio fell or recovered. The record’s stated timeframe is for the duration of the succinylcholine effect, generally expected to be 6-10 minutes. The registry reports the outcome as a mean with standard deviation for the groups that have results.

In general, a mean describes the average endpoint value in a group, while a standard deviation describes the spread of individual measurements around that mean. The posted summaries do not include individual observations, so they do not show the full distribution or whether the measurements were clustered. The record does not report confidence intervals for these means.

The endpoint is a physiological measurement used to characterize fade under train-of-four stimulation. It is not itself a report of a clinical outcome such as a complication or recovery experience. Further details about the measurement equipment, calibration, and handling of repeated measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted results use a continuous endpoint: the lowest recorded ratio of the fourth contraction to the first after succinylcholine administration. For a continuous measure, a group mean gives a compact summary of the recorded values. The standard deviation gives a description of how dispersed those values are around the mean. In this study, each reported group is summarized with a mean and standard deviation, and the registry identifies the parameter as a mean.

What does the mean describe?

The mean is an average of the endpoint measurements in a group. It can be useful for comparing the general level of a continuous outcome across groups, but it does not describe every participant or every measurement time. Here, the endpoint itself is the lowest ratio recorded after administration. Thus, the mean summarizes group values of each participant’s lowest recorded ratio; it is not the mean ratio across all stimulation times. The registry does not provide individual-level observations, so the distribution of the minima cannot be assessed directly.

How should the standard deviation be read?

In general, the standard deviation describes the spread of values around a group mean. A smaller standard deviation indicates that the observed values were more closely clustered around the mean than values with a larger standard deviation. It does not show the uncertainty of the mean as directly as a confidence interval, and it does not indicate whether the underlying distribution is symmetric or contains unusual observations. The reported standard deviations are descriptive, based on the recorded group data.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and a specified statistical procedure, and communicates uncertainty about an estimate. It is distinct from a standard deviation: the standard deviation describes variability among observations, whereas a confidence interval is used to express uncertainty about a quantity such as a population mean or a difference in means. Confidence intervals for the group means and for comparisons are not reported in the registry record. Without them, the precision of the reported means cannot be read directly from the posted results.

Why are group comparisons not available?

The registry record reports no analyses and states that values were missing or not estimable for a two-arm comparison of the continuous endpoint. As a result, there are no reported estimates of between-group differences and no p-values for those comparisons. A difference between displayed means, considered on its own, is not an inferential analysis: it does not account for sampling uncertainty, and it cannot establish whether an observed contrast is distinguishable from random variation. No recalculated comparison should replace an absent sponsor analysis. The record has no sponsor analysis for this outcome to interpret.

In general, a p-value is calculated under a specified statistical model and null hypothesis; it is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of an effect. Because the registry record posts no p-values or test results for the endpoint, statistical significance cannot be assessed from the registry results. A nonreported test is not evidence that groups are equivalent.

How should the planning illustrations be understood?

Any sample-size planning illustration based on the observed effect is a planning calculation, not an observed trial result and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm. They indicate what a calculation under those assumptions might require for a future design, not how much power this completed trial actually had. The registry record does not report the trial’s own sample-size justification, so these planning assumptions should not be treated as its original design rationale.

The effect used in such an illustration is tied to the observed data and therefore may be uncertain, especially with small reported groups. A planning calculation does not resolve the missing arm outcome, the unclear dose-to-arm mapping, or the absence of an inferential comparison. No numerical planning estimates are included in the registry entries described for the posted results, so no participant requirement can be stated from them.

What does the trial structure contribute?

Randomized allocation and a parallel-group structure are registered design features. In general, randomization can support fair comparisons when allocation is implemented as intended and the analysis preserves the randomized groups. The registry record does not describe sequence generation, concealment, analysis populations, or handling of missing outcomes, so those features cannot be evaluated. The unmasked designation also means the registry does not describe the study as masked; additional information on possible masking of outcome measurement is not reported.

Overall, the available statistical evidence is descriptive: group means and standard deviations for the lowest recorded ratio. The record lacks the comparisons and uncertainty estimates needed to quantify inferential evidence for differences among arms. Interpretation should remain at the level of the reported summaries.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Arm 2", "Arm 3", "Arm 4", "Arm 5")
n   <- c(4, 5, 5, 5)
m   <- c(0.85, 0.64, 0.66, 0.68)
sp  <- c(0.02, 0.04, 0.09, 0.04)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Arm 2  4  0.850  0.020  0.818  0.882
CARM  Arm 3  5  0.640  0.040  0.590  0.690
CARM  Arm 4  5  0.660  0.090  0.548  0.772
CARM  Arm 5  5  0.680  0.040  0.630  0.730

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified set of comparisons. The absence of posted secondary outcomes does not establish what outcomes may have been planned or collected outside the registry record. Details of the statistical analysis plan are not reported in the registry record.

Multiplicity arises when several outcomes, groups, time points, or statistical tests are examined. In general, testing many hypotheses can increase the chance of finding an apparently unusual result by chance unless the analysis plan accounts for that testing. The registry does not provide enough information to determine how many comparisons were planned or performed, and it posts no analysis results for the primary outcome. Therefore, no claim about multiplicity control can be made.

The outcome entry for Arm 1 has n=0 and no mean or standard deviation. The record does not explain why outcome results are unavailable for this arm or whether the absence reflects non-enrollment, missing measurement, or another reason. It also does not report participant flow, reasons for missing outcome data, imputation methods, exclusions, or the analysis population. The reported group counts should not be interpreted as a complete account of how participants were assigned, followed, or analyzed.

In general, missing-data handling matters because results can be biased if the chance of an outcome being missing is related to the outcome itself or to group assignment. The registry does not report enough information to assess the missingness mechanism or the robustness of any analysis. Since the two-arm continuous comparison was not estimable, the posted results do not provide a comparative analysis that could clarify these issues.

12. 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.

The registry reports adverse-event group counts separately for serious adverse events and other adverse events. For Arm 2, the serious-event count is 0 among 4 at risk, and the other-event count is 0 among 4 at risk. For Arm 3, both counts are 0 among 5 at risk. For Arm 4, both counts are 0 among 5 at risk. For Arm 5, both counts are 0 among 5 at risk. Arm 1 has zero participants listed at risk and zero events recorded.

These entries mean that no serious or other adverse events are recorded for the listed at-risk groups in the registry results. They do not establish that no events occurred outside the reported collection or reporting period. The registry record does not provide event definitions, collection procedures, ascertainment duration, or further detail about the safety population. No serious-event terms are listed.

In general, a zero event count in a small group does not prove that the underlying event risk is zero. It describes what was recorded in that group, while the uncertainty around an event rate depends on the amount and nature of the safety information. The posted adverse-event figures are descriptive and do not support a broad safety conclusion. Arm 1’s zero at-risk count is not evidence of an absence of events among exposed participants, because no participants are listed at risk for that row.

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

The registry results describe the lowest recorded train-of-four ratio after succinylcholine administration for four arm labels. The reported means are below one, matching the registry’s stated interpretation that a ratio below one reflects more diminution of the fourth contraction than the first. This is a descriptive account of the physiological endpoint recorded in the groups with results.

The results do not establish whether the group means differ beyond what might be expected from sampling variation. No inferential comparison, p-value, or confidence interval is reported, and the registry marks the two-arm continuous comparison as not estimable. The values therefore should not be read as proof of a dose effect or as evidence that groups are equivalent. The arm labels do not specify the dose corresponding to each reported result, which prevents a clear dose-by-dose interpretation.

The endpoint is the minimum ratio recorded during the measurement period, not a full trajectory of the response. It cannot, on its own, show the timing of onset, the course of offset, or how the ratio changed from one measurement to the next. The registry’s study aim includes characterizing onset, offset, and dose effects, but the posted outcome summaries do not report those analyses.

The posted data also do not answer questions about outcomes beyond this measurement, nor do the adverse-event counts establish the absence of risk. The small reported group counts, missing Arm 1 outcome entry, and lack of reported analysis-population details make broader interpretation uncertain. The listed enrollment and outcome entries do not by themselves explain how all enrolled or assigned participants were represented in the results.

The most restrained conclusion is that the record reports group-level endpoint summaries consistent with a T4-to-T1 ratio below one in the arms with outcome data. The record does not provide the comparative statistical evidence needed to quantify differences or support claims about the effect of a particular dose.

14. Why This Trial Matters Statistically

This trial addresses a measurement question in neuromuscular monitoring: whether a depolarizing muscle relaxant can produce fade during train-of-four stimulation. The registry background contrasts the generally expected equal-strength contractions under depolarizing muscle relaxants with evidence that fade may also occur. Measuring the fourth contraction relative to the first makes that phenomenon observable as a continuous ratio rather than relying only on a categorical description.

The endpoint also illustrates how a summary definition affects interpretation. The outcome is the lowest ratio recorded after administration, so it focuses on the strongest recorded fade rather than an average response over time. That choice is relevant to the stated aim of characterizing response during onset and offset, but a minimum alone does not retain the full time course. The record’s endpoint description and analysis results therefore need to be distinguished: the protocol description sets out repeated measurements, while the posted outcome summaries report a group mean and standard deviation for the minimum.

From a statistical perspective, the trial highlights the difference between a descriptive signal and a tested comparison. The reported group means provide a direct summary of the observed measurements, but the absent inferential analyses leave uncertainty about differences between arms. The unavailable control result and unclear mapping of dose descriptions to arm labels further restrict comparisons. Such limitations matter when translating a physiological measurement question into a comparative study result.

The trial is also useful for understanding registry reporting. A completed status and an enrollment figure do not replace arm-level outcome completeness, a transparent analysis population, or estimates of uncertainty. The registry record identifies a primary outcome and reports some group summaries, but does not report the planned sample-size justification or statistical analysis plan. These gaps show why interpretation depends not only on the endpoint value, but also on the design and analysis information accompanying it.

15. 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 posted results have important limits specific to this trial. Arm 1 is identified as the control, but its outcome entry has n=0 and no estimate. The record does not explain why no outcome result is available for that arm. Without a control outcome, the summaries cannot directly characterize the contrast against the registered control group.

The outcome rows are labeled Arm 2 through Arm 5, while intervention descriptions list five dose levels. The registry record does not clearly link each reported arm label to a dose. This prevents reliable interpretation of the reported means as a pattern across dose levels. The listed enrollment is 19, but the record does not explain how that figure relates to the arm-specific outcome entries or identify the analysis population.

The registry posts means and standard deviations but no confidence intervals, p-values, or comparative estimates. It notes that a two-arm comparison was not estimable. This leaves the precision of the group means and the strength of any between-group evidence unquantified. Individual observations and time-course results are not reported, so variation in trajectories and timing of the lowest ratio cannot be assessed.

Further limitations include the unmasked study designation and lack of registry detail on allocation concealment, outcome assessor masking, measurement calibration, missing-data handling, and the statistical analysis plan. The registry record does not report the sample-size justification or the reason the control outcome is absent. The adverse-event entries also lack detailed definitions and ascertainment procedures. These omissions constrain interpretation without establishing that the study was conducted improperly.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fade Upon TOF Stimulation Induced by Succinylcholine — NCT02425449.
• Registry record last updated 2018-01-02; status last verified 2017-12.
• Results first posted 2018-01-02.
• 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.

19. Record Summary

NCT02425449 is a completed randomized, unmasked, parallel-group phase 4 study sponsored by University of Toledo Health Science Campus. The listed enrollment is 19; the recorded start is 2015-04 and primary completion is 2017-01-04.

The study examined fade during train-of-four stimulation after succinylcholine administration. Its primary endpoint was the lowest post-administration ratio of the fourth contraction to the first. The registry reports means and standard deviations for Arm 2 through Arm 5, but no outcome estimate for Arm 1, which is identified as the control. The dose-to-arm mapping is not clear in the result labels.

No secondary outcomes or inferential analyses are posted. The registry states that a two-arm comparison of the continuous endpoint was not estimable. The adverse-event entries record zero serious and other events in the groups with participants listed at risk, with no further event terms listed.