Magnesium vs Placebo for Tonsillectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Magnesium vs Placebo for Tonsillectomy (NCT02218424), a randomized phase 2, phase 3 study. The primary outcome is Postoperative Pain.

2. Clinical Question

3. Trial Design

This completed study is registered as NCT02218424 and is titled “Magnesium vs Placebo for Tonsillectomy.” The official title describes a randomized, double-blinded, placebo-controlled trial of systemic magnesium in pediatric patients undergoing tonsillectomy. The registry classifies the allocation as randomized, the masking as quadruple, and the model as parallel. Its brief summary calls the study double-blind, while the registry’s masking classification is quadruple; which specific groups or roles were masked is not reported in the registry record.

The record lists phase 2 and phase 3. Enrollment was 60, with 30 participants in each reported arm. One arm received intravenous magnesium, with a 30 mg/kg bolus over 15 minutes and a 10 mg/kg/hr infusion through completion of the procedure. The comparator arm received equal-volume intravenous normal saline as placebo. The registry identifies the sponsor as Ann & Robert H Lurie Children's Hospital of Chicago.

The recorded study start is 2014-10, and primary completion is recorded as 2015-04. The status is completed. Randomized allocation and a concurrent placebo group are design features intended to support a fair comparison of assigned groups. Masking can reduce the influence of expectations on care and outcome assessment, although the registry record does not describe how masking was implemented or checked. Further design details—including the sequence-generation method, allocation concealment, protocol deviations, and the sample-size justification—are not reported in the registry record. The posted enrollment should not be taken as evidence of how the target enrollment was chosen.

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 Postoperative Pain, measured over 90 minutes.

The primary endpoint is postoperative pain during a 90-minute period in the post-anesthesia care unit (PACU). The registry describes pain assessments at 15 minute time intervals using the Faces Pain Scale Revised (FPS-R), a validated patient-reported scale from 0 (no pain) to 10 (worst pain imaginable). Rather than treating each assessment as a separate primary outcome, the recorded measure multiplies pain scores by the time spent at each score and combines these contributions as an area under the curve.

This approach is intended to represent pain burden across the measured recovery period: sustained pain contributes differently from a brief score at one assessment. The registry states that the resulting value ranges from 0 to 900, with lower values indicating more favorable and lower pain scores. The endpoint is reported as a median with an inter-quartile range (IQR), a way to describe the center and spread of a distribution without assuming that the mean is the most representative summary. The posted group summaries give medians of 30 for magnesium and 45 for placebo. An IQR value is not populated in the posted primary results, and a formal two-arm comparison is not reported in the registry record. The endpoint’s definition explains what was intended to be measured; it does not by itself establish the completeness or reliability of the recorded assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison. In general, randomization aims to make assigned groups comparable, on average, with respect to both measured and unmeasured factors. A placebo comparator can help distinguish differences associated with assignment to the active intervention from differences related to receiving an infusion or to expectations. These are general principles; the registry record does not report the randomization procedure, concealment method, or checks on masking.

What does the primary summary measure?

The primary outcome is summarized using medians and an IQR, according to the endpoint definition. A median is the central point of an ordered set of observations: half the observations lie at or below it and half at or above it, subject to ties. The IQR describes the middle half of the distribution and is often useful when data are skewed or contain influential extreme observations. These are general explanations of the statistics. In this record, the median values are posted, but an IQR value is not populated. The additional low and high values are not defined in the result fields, so they cannot be interpreted as the IQR.

The outcome itself is an area-under-the-curve measure assembled from repeated FPS-R pain scores and time spent at each score. In general, an area-under-the-curve summary can represent a pattern across a period more fully than a single assessment, but it compresses the repeated measurements into one value. Different patterns of scores over time can produce similar totals. The registry does not report how incomplete or irregular assessment schedules were handled.

Why does a missing comparison matter?

A group summary describes the observed data, while a comparative analysis estimates the contrast between groups and quantifies uncertainty around that contrast. A confidence interval is a range of values compatible with the data and the analysis assumptions; it communicates precision, not the probability that a particular value is true. A p-value is a measure of how unusual data at least as inconsistent with a specified null hypothesis would be under that hypothesis and the analysis model. It is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect.

No formal comparison for the primary endpoint is reported in the registry record. Accordingly, there is no posted primary confidence interval or p-value to interpret. A difference between two medians should not be converted into a claim about statistical evidence without a specified analysis and uncertainty estimate. The record does not report the method used to compare primary outcomes, any adjustment for baseline factors, or any planned analysis model.

How should the secondary comparison be read?

For time to PACU discharge, the posted comparison is a mean difference with a confidence interval and an unadjusted p-value. A mean difference expresses the estimated difference between group means in the outcome’s units; a negative estimate is in the direction of a shorter mean time for magnesium relative to placebo. The confidence interval includes zero, indicating that the posted data do not rule out no mean difference at the stated confidence level. The p-value is unadjusted, so it does not account for examining multiple outcomes. The record does not list a sponsor-reported analysis for this endpoint, and the comparison should be treated as a recalculated, unadjusted result rather than a sponsor-reported conclusion.

In general, standard errors and confidence intervals depend on the observed variation and the analysis assumptions. For a mean comparison, a normal approximation can be used under specified conditions, but the registry does not report a full analysis plan for this outcome. The comparison is not evidence that the arms are equivalent; a non-significant result can reflect uncertainty as well as a small underlying difference.

What do the planning illustrations mean?

The sample-size illustrations are planning calculations based on fractions of the observed secondary effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such figures are hypothetical planning quantities: they show how a future study’s required enrollment could vary under selected effect assumptions and design conditions. They are not observed power, do not describe the power of this completed trial, and do not establish the original study’s intended enrollment. The registry record does not report the trial’s own sample-size justification or design assumptions.

General planning calculations are sensitive to the effect chosen, outcome variability, allocation, significance threshold, and method. An effect estimated from a small study can be imprecise, so basing a future design directly on that estimate can yield unstable planning. The illustrated fractions are scenarios rather than guarantees of a future result. They also do not address missing outcomes, multiplicity, or changes in the analysis plan unless those features are explicitly incorporated.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes in addition to the primary endpoint. When many outcomes are examined, the chance of at least one apparently unusual result can increase. General statistical approaches to this issue include defining a hierarchy of tests, adjusting thresholds, or treating secondary findings as exploratory. The record does not report whether any such multiplicity strategy was planned or used. The posted unadjusted secondary p-value should therefore not be read as if it were adjusted for the full set of outcome questions.

Information about missing data is also limited. The registry reports 30 participants in each arm for the primary outcome summaries and for time to PACU discharge, but it does not report how many participants were randomized, treated, assessed, or included in each analysis beyond those posted group counts. It does not describe withdrawals, incomplete pain assessments, reasons for missing observations, or methods used to handle missing values. The outcome description anticipates repeated PACU pain measurements, but the handling of any missed assessments is not reported in the registry record.

The analysis populations are not identified. The record does not say whether the analyses followed an intention-to-treat principle, included only participants who received assigned treatment, or used another population definition. It also does not report protocol deviations or whether participants were analyzed according to assignment. These omissions prevent assessment of how closely the analyzed groups preserve the randomized comparison.

Further details that can affect interpretation—including prespecified statistical models, covariate adjustment, data transformations, sensitivity analyses, and interim analyses—are not reported in the registry record. Their absence from the record does not establish that such methods were or were not used; it means that their role cannot be assessed from the posted information. The primary outcome’s lack of a reported comparative analysis is especially important: without an estimate and measure of uncertainty, readers cannot judge the precision of the primary contrast or how it was tested.

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.

The posted adverse-event counts report zero serious adverse events and zero deaths in both groups. Each group is listed with 30 participants at risk for serious events and 30 at risk in the other adverse-event category; the recorded affected counts are zero in both groups for those categories. These are counts in the registry’s reported categories, not proof that no adverse experiences occurred outside those classifications or were not captured.

Zero observed events in a group do not establish that the underlying risk is zero. With no events recorded, the registry results cannot provide a comparative estimate of the frequency of rare events or rule out harms that were not observed during the study. Interpretation also depends on how events were defined, collected, monitored, and attributed. Those details, including the duration and completeness of safety follow-up, are not reported in the registry record.

The registry lists respiratory depression and postoperative vomiting among the secondary outcomes, while its adverse-event summary separately reports the affected counts for its event categories. The presence of an outcome name does not itself provide a result for that outcome. The zero counts should therefore be read narrowly as the posted adverse-event figures, rather than as a comprehensive safety assessment or a comparison establishing equivalent safety between the groups.

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

The posted primary summaries describe median PACU pain area-under-the-curve values of 30 for magnesium and 45 for placebo. These figures provide a descriptive account of the recorded group centers on the defined outcome. The registry record does not report a formal comparison for this primary endpoint, an uncertainty interval, or a populated IQR summary. It is therefore not possible to determine from the posted primary results how precisely the group contrast was estimated or whether it is distinguishable from sampling variation.

The time-to-discharge secondary comparison is also uncertain: its confidence interval includes zero, and its p-value is unadjusted. It is one secondary result and does not establish a conclusion about the primary pain endpoint or the other secondary questions. The registry does not provide enough reported secondary analyses to identify a consistent pattern across recovery outcomes.

These results do not establish that magnesium reduces postoperative pain, and they do not establish that it has no effect. A lack of a reported primary comparison is not evidence of no difference. Likewise, a secondary comparison that does not exclude zero is not proof of equivalence. Equivalence or non-inferiority requires a prespecified margin and an analysis designed to assess that question; such information is not reported in the registry record.

The randomized design is relevant because, when implemented and analyzed appropriately, it supports a comparison based on assignment. Yet interpretation also requires information about enrollment, follow-up, missing observations, analysis populations, and methods. Several of these details are not reported. The sample-size planning illustrations are not evidence of the study’s observed power or of a design rationale.

The most defensible reading is limited: the record documents the trial’s question, treatment procedures, posted group summaries, one secondary comparison, and adverse-event counts. It does not provide a complete inferential analysis of the primary endpoint. These registry results alone cannot settle the treatment effect, its precision, or the full safety profile.

13. Why This Trial Matters Statistically

Statistically, this trial is useful as an example of the difference between a clearly defined outcome and a fully reported analysis. The primary endpoint is described in detail: repeated patient-reported pain scores are combined over a specified PACU period into an area-under-the-curve measure, with a stated scale and interpretation. Yet the posted primary results provide group medians without a populated IQR or a reported formal comparison. A precise measurement definition is valuable, but it cannot substitute for a comparative estimate and its uncertainty.

The study also illustrates why design labels alone do not answer every methodological question. Random allocation, a placebo comparator, and masking are important features, but the record does not describe the allocation procedure, exactly who was masked, or the analysis population. Those details help readers assess potential bias and understand whether the analysis preserves the intended comparison. The registry’s quadruple-masking classification and its brief summary’s double-blind wording further show why operational definitions matter.

Another statistical lesson concerns secondary outcomes. A broad set of recovery measures may capture different aspects of the patient experience, but many outcomes raise multiplicity concerns. An isolated unadjusted result should be interpreted as limited evidence rather than as a confirmatory finding. Without reported results across the full set, it is not possible to assess whether outcomes align or conflict.

Finally, planning calculations based on an observed effect are not the same as the trial’s original design justification. A planning illustration can clarify how assumed effects influence a future study’s enrollment needs, but it cannot reveal the original rationale or create evidence about the completed trial’s power. This distinction is important whenever retrospective summaries are used to discuss future research.

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 posted record for this trial. The primary endpoint’s results include group medians but not a populated IQR, and no formal two-arm primary analysis is reported. The additional low and high entries are not defined in the outcome fields, so their interpretation is uncertain. These omissions make it difficult to assess the primary result’s variability or precision.

The registry identifies a 90-minute PACU outcome built from pain scores assessed at 15 minute time intervals, but does not report the number of completed assessments per participant, the handling of missed assessments, or the procedure for forming an area-under-the-curve value when data are incomplete. It also does not report baseline characteristics that would help describe the enrolled population or assess the balance achieved by randomization.

Enrollment is recorded as 60, with 30 participants in each reported arm, but the record does not describe participant flow, withdrawals, treatment adherence, or analysis populations. The study is identified as pediatric, but age criteria and other eligibility details are not reported. The masking classification differs between the registry field and the brief summary, and the roles masked are not specified.

Only one secondary outcome has a posted numerical comparison in the record used for this analysis, and that comparison is unadjusted. Results for other named secondary outcomes are not available in comparable form, while a multiplicity plan is not reported. The safety summary records no events in the listed categories, but event definitions and follow-up details are absent. Finally, the registry does not report the trial’s sample-size justification, complete statistical plan, or interim analyses. These gaps limit both the scope and certainty of interpretation; they do not establish that omitted procedures or analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Magnesium vs Placebo for Tonsillectomy — NCT02218424.
• Registry record last updated 2019-01-03; status last verified 2018-12.
• Results first posted 2018-12-14.
• 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

NCT02218424 is a completed randomized, parallel-group study comparing intravenous magnesium with equal-volume normal saline placebo in pediatric patients undergoing tonsillectomy. Enrollment is recorded as 60, with 30 participants per arm in the posted outcome summaries. The primary outcome is PACU postoperative pain over 90 minutes, summarized as an area-under-the-curve measure from repeated FPS-R scores. The posted median values are 30 for magnesium and 45 for placebo, but the registry record does not report a formal primary comparison or populate the IQR summary.

Time to PACU discharge is the one secondary outcome with a posted numerical comparison; it is an unadjusted result. The record names additional secondary outcomes but does not provide a complete comparable analysis across them. Serious adverse events and deaths are reported as zero in each group. Key information about missing data, analysis populations, multiplicity, and the primary analysis method is not reported in the registry record. The posted information therefore describes the study and selected results but does not provide a complete inferential assessment of its primary question.