Quality of Recovery After Reversal With Neostigmine or Sugammadex.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quality of Recovery After Reversal With Neostigmine or Sugammadex. (NCT02909439), a randomized phase 4 study. The primary outcome is Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes.

2. Clinical Question

The study compares recovery measures after reversal of neuromuscular blockade with two medications. Its primary endpoint is a change-from-baseline measure, so the posted values describe the direction and magnitude of change within each arm at a specified recovery time. They do not, on their own, estimate the treatment difference or establish whether any difference is compatible with chance variation.

The registry reports median incentive spirometry changes at 30 minutes: -700 mL in the neostigmine arm and -862 mL in the sugammadex arm. It also gives an inter-quartile range for each median. These are summaries of the observations available for the measure, not a reported test of the arms against one another. The record notes that some patients could not perform the measure at this time point because of significant sedation or significant pain, which is relevant to who contributed data.

The clinical question therefore has two parts: what recovery was observed in each arm, and whether the randomized comparison supports a reliable difference between arms. The first part has descriptive summaries in the registry. A formal primary comparison, its uncertainty, and its analysis method are not reported in the registry record.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group phase 4 study sponsored by Stony Brook University. It lists an enrollment of 80 and a completed status. The study dates recorded are a start in 2016-11 and primary completion on 2017-11-09. These are registry entries and do not, by themselves, describe how many participants contributed data to each outcome.

One arm received neostigmine and the other received sugammadex for reversal of neuromuscular blockade. The parallel design means the registry describes separate groups receiving the respective interventions, rather than a crossover in which participants receive both. The allocation ratio and the specific parties masked are not reported in the registry record. “Single” masking is recorded, but the registry information does not identify who was masked or how masking was maintained.

The brief summary says that recovery measures after surgery include pulmonary function, muscle strength, time to extubation, and quality of recovery in the post-anesthesia care unit. The registry lists incentive spirometry at several time points as a measure of pulmonary function. Secondary outcomes include grip strength at 30, 60, and 120 minutes, time to extubation, train-of-four recovery during PACU admission, a Quality of Recovery 15 survey, and time to readiness for PACU discharge.

The reported enrollment is not interchangeable with the number analyzed for a particular endpoint. For the primary 30-minute measure, the registry gives 21 participants in the neostigmine arm and 18 in the sugammadex arm. The registry explains that the gap between participant flow and the analyzed count reflects inability to perform the measurement at that time point because of significant sedation or pain. Outcome-specific counts differ for the secondary measures as well. A detailed participant-flow account and the reasons for all other differences are not reported in the registry record.

The registry does not report the trial's sample-size justification, the randomization procedure, concealment details, or a prespecified statistical analysis plan. Those omissions limit assessment of design and analysis choices beyond the basic design labels and results recorded.

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.

Before assignment: 18 patients were excluded after enrollment. The reasons were (1) no longer met inclusion criteria (n =10), declined to participate (n=3), change in surgical date \& logistical issues (n=5)

Overall Study

Analysis population for the primary outcome, as defined in the registry: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain

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 Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes, measured over 30 Minutes.

The primary endpoint is incentive spirometry change from baseline at 30 minutes, reported in milliliters as a median with an inter-quartile range. The registry says measurements were planned at 30, 60, and 120 minutes after surgery, and describes the endpoint as part of a recovery profile. The listed primary result concerns the 30-minute time point.

Incentive spirometry is used in this study as a measure related to pulmonary function during postoperative recovery. A change-from-baseline outcome expresses how a measurement at follow-up differs from its baseline reference; the registry does not provide further detail about the baseline procedure or the spirometry protocol. A negative change indicates a value below baseline on the recorded change scale, but the registry does not define a threshold for clinical importance.

The neostigmine arm has a median change of -700 mL, with an inter-quartile range from -1650 mL to -250 mL. The sugammadex arm has a median change of -862 mL, with an inter-quartile range from -1800 mL to -500 mL. These summaries describe the observed distributions among participants with an available measurement. They do not provide a direct estimate of the difference between treatment arms or its precision.

The record explains that patients could be unable to perform the measure at this time point because of significant sedation or significant pain. This matters because a measurement that cannot be obtained is not simply a value at either end of the observed range. The extent to which unavailable measurements affect interpretation cannot be determined from the posted primary summaries alone. The registry does not report an imputation method or a primary between-arm analysis for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Understanding these results requires separating descriptive summaries, comparative estimates, uncertainty, and planning illustrations. They answer different statistical questions and should not be treated as substitutes for one another.

What does a median with an inter-quartile range describe?

General statistical explanation: a median is the central value of an ordered set of observations. The inter-quartile range describes the span from the first quartile to the third quartile, enclosing the middle half of the observed values. It communicates the spread of the measurements without assuming that the data follow a symmetric distribution. For the primary endpoint, the registry reports medians and inter-quartile ranges rather than means and standard deviations.

The two arm-specific medians do not themselves give a median treatment difference. Subtracting arm medians would create a quantity that is not necessarily the median of participant-level differences, and the registry does not report such a contrast. Nor does overlap or non-overlap of inter-quartile ranges replace a formal comparison. A comparative analysis would need to specify the estimand, method, and uncertainty measure; these details are not reported for the primary outcome.

What do the grip-strength confidence intervals mean?

General statistical explanation: a confidence interval expresses uncertainty around an estimated effect under the assumptions of the analysis. A wider interval indicates less precision than a narrower interval, all else equal. A confidence interval that includes zero for a mean difference is compatible with no difference as well as with some positive or negative differences within its bounds. It is not proof that the true difference is zero.

The grip-strength intervals are based on unadjusted recalculations from posted arm-level means, standard deviations, and sample sizes. They are not described as sponsor-reported analyses, and the registry reports no analyses for those outcomes. Their scope is therefore limited to simple comparisons based on the available summaries. The registry does not report covariate adjustment, repeated-measures modeling, or a method to account for multiple secondary comparisons.

A p-value is a measure of how incompatible observed data are with a specified null model, under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, nor does it quantify the importance of an effect. The grip-strength p-values are explicitly unadjusted. Because multiple secondary outcomes and time points are listed, their interpretation should not be detached from the broader analysis context. The registry does not report a multiplicity strategy or identify which secondary comparisons, if any, were prespecified as confirmatory.

Why can unavailable measurements matter?

General statistical explanation: missing outcome data can reduce precision because fewer observations contribute to an analysis. It can also affect the interpretation of an estimate if the probability of obtaining a measurement is related to the outcome or to other participant characteristics. Missingness that occurs for reasons related to sedation or pain is especially important to describe because those circumstances may be connected to the ability to complete a recovery measurement. This does not establish that the missing values biased the result; it means the available summaries alone cannot rule out that possibility.

The registry states that some patients could not perform the primary measurement because of significant sedation or pain. It does not report the number of such cases, an arm-specific breakdown, a missing-data assumption, or an imputation or sensitivity analysis. Consequently, the primary summaries are best understood as describing participants with measured values, not necessarily all randomized participants.

Why is over-dispersion relevant?

General statistical explanation: over-dispersion arises when observed variability exceeds what a statistical model expects. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. It is relevant in some count-data analyses, particularly when a simple distribution assumes a tighter relationship between the mean and variance than the data support. The registry results do not report a count-data comparison or an over-dispersion adjustment, so this issue cannot be evaluated for the primary endpoint or the posted grip-strength calculations.

How should planning illustrations be read?

General statistical explanation: a sample-size calculation asks how many observations a future study might need under stated assumptions to detect a chosen effect with a chosen probability, often called power. Such a calculation depends on the assumed effect, variability, allocation, significance level, and statistical method. It is not a measure of the probability that the completed study detected an effect, and it cannot retroactively establish that the observed study had adequate power.

The registry includes planning illustrations based on fractions of observed effects, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations for continuous outcomes report participants per arm. They are explicitly not the trial's own design calculation. Since an observed effect can be uncertain, using it as a planning assumption does not make it a reliable target for a future trial. The trial's original sample-size assumptions and justification are not reported in the registry record.

Finally, enrollment and analyzed sample size answer distinct questions. Enrollment describes the registry's recorded study enrollment, whereas the endpoint-specific counts indicate how many observations contributed to particular summaries. Neither one alone identifies the analysis population, whether all randomized participants were retained in the analysis, or how missing observations were handled. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary recovery outcomes, including repeated grip-strength time points and measures recorded during PACU recovery. When multiple outcomes or time points are tested, the chance of at least one apparently unusual result can increase if each test is interpreted separately without adjustment. General statistical explanation: multiplicity methods can control or otherwise address this issue, but the appropriate approach depends on which outcomes are confirmatory, how they are ordered, and what question the study is designed to answer.

A multiplicity strategy, hierarchy of outcomes, or distinction between confirmatory and exploratory secondary tests is not reported in the registry record. The grip-strength p-values are unadjusted recalculations. They should therefore not be interpreted as if they were adjusted for the full set of outcomes or time points. The registry lists 10 outcome measures and seven posted secondary outcomes, but does not provide a complete analysis plan linking these measures to statistical hypotheses.

There is also incomplete reporting of analysis populations and missing outcomes. For the primary 30-minute incentive spirometry endpoint, the registry states that patients unable to perform the measurement because of significant sedation or significant pain account for the difference between participant flow and the analyzed count. The arm-level counts are 21 for neostigmine and 18 for sugammadex. The number unable to complete the measure, the arm-specific reasons, and the way missing values were handled are not reported in the registry record.

Outcome-specific sample sizes are also different for grip strength across its reported time points. These differences mean that each summary describes the observations available for that endpoint, rather than a common complete-data group. The registry does not report whether an intention-to-treat population, per-protocol population, or another analysis population was specified, nor whether any sensitivity analyses were conducted.

These omissions do not establish that the analyses were inappropriate. They limit what can be concluded from the registry record: the primary analysis cannot be reconstructed, missing-data assumptions cannot be assessed, and the family-wise interpretation of secondary findings is unknown. The record also does not report interim analyses or a statistical analysis plan, so neither should be presumed to have occurred or not occurred.

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 reports serious adverse events in 0 of 31 participants at risk in the neostigmine group and 0 of 31 participants at risk in the sugammadex group. It reports other adverse events in 2 of 31 participants at risk in each group. Deaths are reported as 0 in both groups.

These are descriptive counts for the registry's adverse-event categories. They do not establish that the groups have identical safety profiles or that an event cannot occur. With no serious adverse events recorded in these groups, the registry counts do not provide a comparative estimate of the rate of rare serious events. The counts also do not describe event severity, timing, duration, or relatedness to treatment beyond the categories reported.

The record does not list serious adverse-event terms. It gives the same at-risk count for the two adverse-event categories in each group, but the safety counts should not be treated as the endpoint-specific efficacy analysis population. The registry's adverse-event summaries alone cannot establish causation or provide a complete assessment of safety.

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

The posted primary summaries describe a decline from baseline in incentive spirometry at 30 minutes in both treatment arms. The median change is -700 mL for neostigmine and -862 mL for sugammadex, with the reported inter-quartile ranges reflecting variation among the measured participants. These values describe the recorded endpoint; they do not determine whether the treatments differ in a statistically reliable or clinically important way.

No primary between-arm estimate, confidence interval, or p-value is reported in the registry record. Without such an estimate, the primary results cannot establish superiority, inferiority, or equivalence. A difference between two arm-specific medians is not itself a tested treatment effect. The registry also does not report a threshold defining a clinically important change in incentive spirometry.

The secondary grip-strength recalculations show imprecise unadjusted estimates, with confidence intervals that include zero. They are not proof of no effect, and they do not establish that any potential difference would be important to patients. Other listed secondary outcomes have no numerical results available for interpretation in this record. The safety counts are similarly descriptive and should not be read as evidence that risks are identical.

The study is recorded as randomized and parallel-group, which is relevant to the design of the comparison, but the registry record does not provide enough analysis detail to assess all consequences of that design. In particular, missing primary measurements, outcome-specific sample sizes, lack of a reported analysis plan, and absence of multiplicity details limit inference. These limitations do not invalidate the observed measurements; they define the scope of conclusions that can be drawn from them.

Accordingly, the registry supports a cautious account of the observed recovery summaries, not a treatment recommendation. The available results do not settle whether either reversal medication produces better pulmonary or overall postoperative recovery. That question would require a reported comparative primary analysis, clear handling of unavailable data, and adequate information about the planned analysis and clinically meaningful effects.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between describing outcomes and estimating a treatment effect. The primary result gives an arm-specific median and inter-quartile range, but no primary contrast or uncertainty interval. Readers can see the observed distributions' central summaries, yet cannot use them alone to determine how precisely the treatment groups differ.

It also illustrates why endpoint-specific denominators matter. The registry's enrollment is 80, while the 30-minute primary summaries use 21 participants in the neostigmine arm and 18 in the sugammadex arm. The registry attributes the discrepancy from participant flow to inability to perform the measure because of significant sedation or pain. A recovery outcome that cannot be obtained for some patients raises a statistical question about the analysis population and missing-data assumptions, not merely a bookkeeping issue.

The secondary grip-strength data offer simple comparisons with confidence intervals, but their unadjusted status and the presence of multiple outcomes limit confirmatory interpretation. The posted p-values do not replace a prespecified analysis strategy, and a set of secondary measures should not be treated as one unified recovery endpoint without an analysis that defines how they relate.

Finally, the record contains planning illustrations based on observed effects, but explicitly distinguishes them from the study's own design calculation. This is a useful reminder that retrospective planning estimates are not observed power and do not prove that a completed study was adequately powered. The original sample-size rationale is not reported. Together, these features make the record a case study in how reporting detail, missing data, and multiplicity affect the strength of statistical conclusions.

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 are specific to the information recorded for this study. The primary outcome is reported with arm-level medians and inter-quartile ranges, but there is no posted treatment contrast, confidence interval, or p-value. This prevents a direct assessment of the primary comparative question and leaves the method used to analyze the outcome unknown.

The registry identifies inability to perform the primary measure because of significant sedation or significant pain, but it does not report the number of affected patients or their distribution between arms. It also does not describe imputation, sensitivity analysis, or other missing-data handling. Because these reasons relate to the conditions under which a recovery measurement can be obtained, the available summaries may not represent all randomized participants in a way that can be evaluated from the record.

There is no reported detail about the spirometry measurement protocol, the baseline procedure, or a threshold for clinical importance. The meaning of the recorded changes can therefore be described on the registry's measurement scale, but not translated into a judgment about clinical importance using information in the record.

For secondary outcomes, numerical comparisons are available for grip strength only. The remaining listed outcomes, including extubation time, train-of-four recovery, quality of recovery, and PACU discharge readiness, cannot be assessed from numerical results in this record. The grip-strength comparisons are unadjusted recalculations, and the registry does not report a multiplicity plan, analysis populations, or an analysis plan.

Trial-design details are also limited: the specific parties masked, allocation ratio, randomization method, and sample-size justification are not reported in the registry record. These gaps restrict evaluation of the conduct and analysis beyond the recorded randomized, single-masked, parallel design. They should be treated as reporting limitations, rather than evidence that a particular procedure was or was not used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Quality of Recovery After Reversal With Neostigmine or Sugammadex. — NCT02909439.
• Registry record last updated 2020-05-22; status last verified 2020-05.
• Results first posted 2020-05-22.
• 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 record describes NCT02909439, a completed, randomized, single-masked, parallel-group phase 4 study sponsored by Stony Brook University. It records enrollment of 80 and compares neostigmine with sugammadex for reversal of neuromuscular blockade after surgery.

The primary outcome is incentive spirometry change from baseline at 30 minutes, reported as a median with an inter-quartile range. The analyzed counts are 21 for neostigmine and 18 for sugammadex. The record attributes the difference between participant flow and analyzed counts to patients being unable to perform the measure because of significant sedation or pain. No primary between-arm analysis is reported.

Three grip-strength outcomes have posted arm summaries and unadjusted recalculated comparisons. Other listed secondary outcomes do not have numerical results available in this record. The adverse-event summaries report no serious adverse events or deaths in either group, and two other adverse events in each group. The registry does not report the original sample-size justification, a complete analysis plan, multiplicity handling, or missing-data methods.