Relation Between TOF-Watch® SX and a Peripheral Nerve Stimulator After 4.0 mg.Kg-1 Sugammadex (P05698): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Relation Between TOF-Watch® SX and a Peripheral Nerve Stimulator After 4.0 mg.Kg-1 Sugammadex (P05698) (NCT00535496), a randomized phase 3 study. The primary outcome is Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX.

2. Clinical Question

The trial question is about agreement or correspondence between two measurements of neuromuscular recovery, rather than whether sugammadex is better than another treatment. The trial description refers to sugammadex given after either a bolus dose of 0.6 mg/kg rocuronium or the last maintenance dose of 0.15 mg/kg rocuronium. It does not report separate primary endpoint results for those rocuronium circumstances.

The primary endpoint itself is the time from the start of 4.0 mg/kg sugammadex administration until the TOF-Watch® SX T4/T1 ratio reaches 0.9. The PNS observation is described as the time to manual detection of the reappearance of T4. The objective is to relate those times within an individual, not to treat the forearms as independent participants. The registry record does not report the observed times, the magnitude of the within-participant relationship, or an estimate of uncertainty around that relationship.

3. Trial Design

This was a phase 3, randomized, parallel-group trial with no masking. The registry reports enrollment of 91 participants and a completed status. The recorded trial dates are start 2007-09 and primary completion 2008-01. The sponsor was Merck Sharp & Dohme LLC. The condition listed is neuromuscular blockade.

The intervention was sugammadex. Four arm descriptions combine two dose levels, 1.0 mg/kg and 4.0 mg/kg, with alternative placement of the TOF-Watch® SX and PNS across the dominant and non-dominant forearms. The primary endpoint description focuses only on participants receiving 4.0 mg/kg. It reports TOF-Watch® SX measurements from the dominant forearm for n =30 and from the non-dominant forearm for n = 31. The registry says the 1.0 mg/kg group was not evaluated for this endpoint.

For the primary endpoint, the devices were used on separate forearms to reduce the possibility that the device placement itself would bias the measurement. The forearm measurements were not analyzed as a difference between dominant and non-dominant sides. Instead, the stated objective was to assess the within-participant relationship between the time of PNS-detected T4 reappearance and the time the TOF-Watch® SX ratio reached its threshold.

The registry record does not report the number randomized to each arm, the allocation sequence generation method, or details of concealment. It does report randomization, but random allocation alone does not establish that an allocation sequence was concealed. The study was unmasked. The registry does not report a protocol-level explanation of the parallel model or further details about how participants were assigned among the dose and forearm-placement groups.

Although enrollment was 91, the primary endpoint description gives measurement counts by forearm rather than a single count for a two-group treatment comparison. One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed for that outcome. The registry record does not provide a participant flow accounting for all enrolled participants across treatment, measurement, and analysis populations.

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: The Intent-To-Treat (ITT) population: randomized, received 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed. One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed.The 1.0 mg/kg group was not evaluated.

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 Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX, measured over Up to 4 minutes after administering sugammadex.

The primary endpoint is the time from the start of 4.0 mg/kg sugammadex administration to recovery of the T4/T1 ratio to 0.9, measured with a TOF-Watch® SX. The endpoint is recorded in minutes, with a stated timeframe of up to 4 minutes after sugammadex administration. It is a continuous measure, and the registry identifies its summary as a mean with a standard deviation.

To obtain the measure, repeated train-of-four electrical stimulations were applied to the ulnar nerve every 15 seconds, and the twitch response was assessed at the adductor pollicis muscle. T1 and T4 are the heights of the first and fourth twitches after stimulation. The T4/T1 ratio therefore expresses the fourth twitch relative to the first. In the registry description, a higher ratio indicates a lower degree of neuromuscular blockade, and 1.0 represents full recovery.

The threshold of 0.9 defines the recovery point used to time the endpoint. This gives the measurement a specific operational meaning: it records when the device-measured ratio reaches the defined threshold, rather than a broader clinical outcome. The paired PNS measure concerns manual detection of the reappearance of T4. The intended statistical question is whether the time identified by one method corresponds to the time identified by the other within participants.

The endpoint is relevant to the study objective because it makes both measurement methods refer to recovery after the same intervention. However, the registry record does not report the mean, standard deviation, distribution, or within-participant relationship estimate. It therefore describes how the endpoint was defined, but not the observed timing results or the precision of those results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous time measure: the elapsed time from the start of sugammadex administration until a device-measured ratio reaches a threshold. For continuous data, a mean describes the average observed value, while a standard deviation describes how spread out individual measurements are around that average. The registry identifies those as the intended summary statistics, but does not report their numerical values. The average and spread therefore cannot be interpreted from the registry record.

The measurement procedure uses train-of-four stimulation. In general, repeated stimulation produces a sequence of twitch responses, and the relative size of the fourth response compared with the first can be used to describe recovery. In this trial, T4/T1 was followed until it reached 0.9. The registry states that a ratio of 1.0 represents full recovery and that a higher ratio indicates a lower degree of neuromuscular blockade. These descriptions explain the meaning of the measurement; they do not provide evidence about the observed results.

The endpoint includes two measurement approaches: a TOF-Watch® SX reading and manual PNS detection of T4 reappearance. The stated scientific aim is to assess their relationship within each participant. For paired data, each participant contributes measurements that are linked to one another. In general, analyses of paired measurements should preserve that link; treating paired observations as independent would fail to account for their shared participant. The registry describes the within-participant objective but does not report the statistical method used to estimate the relationship.

Association and agreement are related but not interchangeable concepts. In general, two methods can move together while still producing systematically different readings. An association statistic addresses whether higher values by one method tend to occur with higher values by another. An agreement analysis asks how close the paired measurements are and whether any systematic offset or pattern of disagreement is present. The registry record does not specify which of these properties was formally assessed, and it reports no estimate that would allow readers to judge either property.

A confidence interval, in general, gives a range of values compatible with the data and the assumptions of the analysis. Its width conveys precision: a narrower interval indicates greater precision than a wider interval, all else being equal. No confidence interval for the primary endpoint or for the relationship between methods is reported in the registry record. A p-value, in general, evaluates how compatible data are with a stated null hypothesis under a specified statistical model; it does not measure the size or practical importance of an effect. No primary endpoint p-value is reported.

The registry identifies the primary endpoint summary as mean and standard deviation, but that does not by itself describe a complete analysis plan. The outcome title and description do not specify a model for paired measurements, a correlation or agreement statistic, adjustment variables, handling of outliers, or a method for uncertainty estimation. Those details are not reported in the registry record. It is therefore not possible to reproduce or assess the intended primary analysis from the endpoint definition alone.

The record gives two forearm measurement counts for the 4.0 mg/kg dose group: n =30 for the dominant forearm and n = 31 for the non-dominant forearm. It states that dominant and non-dominant forearm differences were not analyzed, because forearm placement was intended to prevent bias. These counts describe device-placement measurements; they should not be mistaken for the sizes of two independent treatment arms. The record does not say whether every participant contributed a complete paired PNS and TOF-Watch® SX observation.

One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed for the endpoint. This is important because a threshold-based time outcome may be unavailable for a participant who does not reach the threshold within the observation period. In general, excluding such participants can affect the interpretation of a mean time among those analyzed, especially if reaching the threshold is associated with participant characteristics or recovery timing. The record does not report the observation period for such a participant, a rule for assigning a value, or a sensitivity analysis.

Sample-size calculations based on an observed effect are planning illustrations, not observed power. In general, such illustrations ask how many participants per arm might be needed under stated assumptions to detect a chosen fraction of an effect. The assumptions noted for this trial's planning illustration include a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The registry record does not report the trial's own sample-size justification. Nor does it report numerical planning outputs in the record. Such planning values, when available, should not be treated as evidence that the completed trial had a particular probability of finding a result.

Over-dispersion is a general issue when observed variation exceeds what a statistical model assumes. In a continuous outcome analysis, an incorrect assumption about variability can make uncertainty estimates unreliable. The registry record does not describe an over-dispersion assessment or any model for the primary relationship, so no trial-specific statement about this issue can be made.

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("Sugammadex 4.0 mg/kg")
n   <- c(60)
m   <- c(1.5)
sp  <- c(0.7)
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  Sugammadex 4.0 mg/kg  60  1.500  0.700  1.319  1.681

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analysis entries. It does not report a multiplicity strategy for handling several outcomes or possible analyses. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase; a prespecified hierarchy or adjustment can help address that issue. The registry record does not say whether outcomes were ordered, whether adjustments were planned, or how the primary endpoint was distinguished analytically from other outcomes.

The primary endpoint description identifies an Intent-To-Treat population as randomized participants who received 4.0 mg/kg sugammadex and had at least one efficacy measurement. That definition includes a post-randomization requirement to receive treatment and have a measurement, so it is not equivalent to a population defined solely by randomization. The record does not report whether other analysis populations were used or how participants were handled across them.

One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed for the endpoint. The registry does not report whether this was the only missing primary endpoint measurement, why the participant did not reach the threshold, or how missing or incomplete paired measurements were handled. It also does not describe an imputation method, a sensitivity analysis, or assumptions about the missingness process. These details are not reported in the registry record.

In general, missing outcome data can affect both the estimated average and its uncertainty, particularly when the chance of missingness is related to the unobserved outcome. The available description is not enough to determine whether the analyzed endpoint measurements represent all randomized participants receiving the target dose. No protocol, statistical analysis plan, interim analysis plan, or explanation of multiplicity procedures is reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peritonitis (1.6%), perforation bile duct (1.6%), procedural complication (1.6%), bladder disorder (1.6%), urinary retention (1.6%).

The registry reports serious adverse events for two dose groups. In the Sugammadex 1.0 mg/kg group, 0 serious adverse events were reported among 29 participants at risk. In the Sugammadex 4.0 mg/kg group, 3 serious adverse events were reported among 61 participants at risk. The record reports other adverse events in 24 participants among 29 at risk in the 1.0 mg/kg group, and in 53 participants among 61 at risk in the 4.0 mg/kg group.

These are counts of participants with events relative to the group sizes listed as at risk. They are not the primary endpoint, and they do not describe the measurement relationship between PNS and TOF-Watch® SX. The registry lists Peritonitis, Perforation bile duct, Procedural complication, Bladder disorder, Urinary retention, and Rash erythematous among the top serious terms, each recorded as 1.6%. The record does not establish from these figures whether any event was caused by study treatment.

Deaths are not reported in the registry record. The available information does not provide further detail on event timing, severity beyond the serious-event classification, or how events were adjudicated. The figures should therefore be read as reported safety counts, not as a complete account of clinical context or comparative risk.

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

The trial addresses a focused statistical question: whether time to manual PNS detection of T4 reappearance relates to the time for a TOF-Watch® SX T4/T1 ratio to reach 0.9 within the same participant after 4.0 mg/kg sugammadex. The registry describes the measurement methods, the recovery threshold, and the population intended for the endpoint. It also records the trial as randomized, parallel, unmasked, and completed.

What the available record does not establish is the strength, direction, or precision of the relationship between the methods. No mean or standard deviation for the primary endpoint, paired-method estimate, confidence interval, or p-value is reported. Without those results, readers cannot evaluate the observed timing, its variability, or how closely the methods corresponded in participants.

The described endpoint is not a comparison of the 1.0 mg/kg and 4.0 mg/kg doses. Although both dose levels appear in the arm descriptions, the registry says the 1.0 mg/kg group was not evaluated for the primary endpoint. Nor is the endpoint a randomized comparison between the two forearms: the forearms were used for device placement, and their differences were not analyzed.

The record also does not establish that either measurement method is superior, that the measurements are interchangeable, or that a particular treatment outcome follows from reaching the ratio threshold. Those conclusions would require results and analyses that are not reported. The endpoint is a measurement of recovery timing, not a direct measure of a broader patient outcome.

In general, a well-defined endpoint can clarify what a trial intended to measure, but the definition alone cannot substitute for the results. Here, the registry supports interpretation of the intended question and data collection approach. It does not support a quantitative conclusion about the answer to that question.

14. Why This Trial Matters Statistically

This trial is statistically notable for asking a measurement question rather than a conventional treatment-versus-control question. The primary objective concerns whether two ways of identifying neuromuscular recovery give related times within the same participant. That structure matters because observations from two devices or forearms in one person are paired, not independent. The analysis should reflect that pairing if it is to estimate the stated within-participant relationship.

The endpoint also illustrates the importance of operational definitions. The TOF-Watch® SX outcome is tied to a specific ratio threshold, while the PNS measure is based on manual detection of T4 reappearance. Defining both methods and the time origin makes the intended comparison more concrete. Yet a carefully specified endpoint still needs an explicit statistical analysis and reported results before readers can judge correspondence or precision.

The registry's forearm-placement descriptions highlight a design consideration: device position was varied between dominant and non-dominant forearms, with the aim of preventing bias. The record says these forearm differences were not analyzed. This reinforces the need to distinguish the role of a design feature from a planned treatment comparison; the forearms are not separate randomized treatment arms for the primary endpoint.

The record also illustrates the limits of interpreting a completed trial from endpoint definitions alone. Enrollment and endpoint measurement counts are reported, and the registry identifies a participant who did not reach the threshold and was excluded from endpoint analysis. However, numerical outcome estimates and details about missing-data handling are not reported. Those omissions constrain assessment of both the result and its uncertainty.

For clinical researchers and statisticians, the central lesson is that the research question, measurement process, analysis population, and statistical results must be considered together. In this case, the question and measurement plan can be described, but the registry record does not provide the quantitative evidence needed to determine how the two measurement times related.

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 main limitation for statistical interpretation is that the registry record does not report numerical results for the primary endpoint. Although it specifies a mean and standard deviation as the summary, neither is listed. The record also gives no estimate of the within-participant relationship between PNS detection time and TOF-Watch® SX recovery time, and no confidence interval or p-value is reported.

The endpoint population and measurement counts are not fully reconciled with the total enrollment of 91. The description reports n =30 for the dominant forearm and n = 31 for the non-dominant forearm in the 4.0 mg/kg group. One participant who did not reach the 0.9 threshold was not analyzed. The registry does not provide a complete participant flow or state whether other measurements were missing or incomplete.

The primary endpoint is restricted to participants treated with 4.0 mg/kg sugammadex; the 1.0 mg/kg group was not evaluated for it. As a result, the endpoint description cannot support a dose comparison. The registry also says forearm differences were not analyzed, so it does not provide a comparison of dominant and non-dominant sides.

The registry record does not report the statistical method for the within-participant relationship, the treatment of incomplete paired observations, a missing-data sensitivity analysis, or an analysis plan for multiple outcomes. It does not report the trial's own sample-size justification. These gaps limit reproducibility and prevent assessment of whether the analysis addressed the intended measurement question as planned.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Relation Between TOF-Watch® SX and a Peripheral Nerve Stimulator After 4.0 mg.Kg-1 Sugammadex (P05698) — NCT00535496.
• Registry record last updated 2015-03-17; status last verified 2015-02.
• Results first posted 2013-09-02.
• 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

This completed phase 3 trial enrolled 91 participants and was randomized, parallel, and unmasked. It studied sugammadex after rocuronium and focused its primary endpoint on time to a TOF-Watch® SX T4/T1 ratio of 0.9 after 4.0 mg/kg sugammadex. The stated objective was to relate that time to manual PNS detection of T4 reappearance within participants.

The endpoint description reports measurements by forearm and says the 1.0 mg/kg group was not evaluated for this outcome. One participant who did not reach the threshold was not analyzed. Although the registry identifies the endpoint summary as a mean with standard deviation, it does not report numerical primary endpoint results or a statistical estimate of the relationship between methods. It also does not report the analysis details needed to assess that relationship. Safety counts are listed separately for the two dose groups.