Maxigesic IV Phase 3 Bunionectomy Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maxigesic IV Phase 3 Bunionectomy Study (NCT02689063), a randomized phase 3 study. The primary outcome is Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm)..

2. Clinical Question

The study was designed to assess clinical efficacy and safety after bunionectomy. Its four parallel groups allow the combination treatment to be considered alongside placebo and alongside each of its individual drug components. The primary endpoint summarizes pain-intensity change over time rather than relying on a single pain rating. This is intended to represent the course of reported pain during the observation period, with the endpoint calculated through the first pre-rescue pain assessment when rescue medication was used.

The registry record describes the primary analysis population as all randomized participants who received the first study dose under staff supervision. It does not provide a separate estimand describing how rescue medication, discontinuation, or other post-randomization events were handled beyond the endpoint rule for rescue medication. Nor does it report a primary contrast or a prespecified threshold for a clinically important difference. The posted primary group summaries therefore describe the recorded endpoint by group; they do not by themselves establish the result of a formal comparison.

3. Trial Design

NCT02689063 is a completed Phase 3 randomized, double-blind, parallel-group study with placebo control. The registry lists 276 participants enrolled and four treatment groups: Maxigesic IV, IV acetaminophen, IV ibuprofen, and placebo IV. The study addressed postoperative pain following bunionectomy. Its stated purpose was to determine the clinical efficacy and safety of the combination treatment and the individual active treatments against placebo.

The combination group received intravenous acetaminophen 1000 mg plus intravenous ibuprofen 300 mg in a 100 mL infusion every 6 hours for 48 hours. The acetaminophen group received 1000 mg in a 100 mL infusion on the same schedule, and the ibuprofen group received 300 mg in a 100 mL infusion on that schedule. The placebo group received 100 mL saline by infusion every 6 hours for 48 hours. The record identifies the study as double-blind but does not specify the masking procedures or which roles were masked.

The registry lists 75 participants in the Maxigesic IV group, 75 in the IV acetaminophen group, 76 in the IV ibuprofen group, and 50 in the placebo group for the posted outcome summaries. The primary efficacy population is described as all randomized participants who received the first dose under study staff supervision. The registry record does not report how the allocation sequence was generated, how it was concealed, or why the group sizes differ.

The study started on 2016-10-26, reached primary completion on 2017-06-30, and is marked completed. The sponsor is AFT Pharmaceuticals, Ltd. The record does not report a sample-size justification or a statistical analysis plan, so the basis for the planned enrollment and the intended primary comparison cannot be assessed from this record alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants randomized (276 in total) received the first dose of study medication under study staff supervision were included in the primary efficacy endpoint analysis.

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 Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm)., measured over 48 hours after the first dose.

The primary endpoint is summed pain-intensity difference over 48 hours after the first dose, expressed as a score on a scale. The registry describes pain-intensity difference as baseline pain intensity minus a later visual analogue scale score. Repeated differences are combined as the area under the curve, called SPID; a higher pain-intensity difference indicates greater reported relief. For the primary endpoint, the SPID is adjusted by the time from baseline to the final pain score used, yielding a time-adjusted SPID48 in millimetres.

This type of endpoint is used to capture a pain-relief profile across the observation period rather than treating one rating as a complete account of pain experience. Repeated assessments can reflect both the magnitude and duration of changes in reported intensity. The registry also states that, if a participant required rescue medication, the SPID was calculated through the first pre-rescue pain assessment, inclusive. That rule defines how rescue medication affects the endpoint window, although the record does not explain how rescue use was incorporated into a treatment-effect estimand.

The posted primary summaries report means and describe dispersion as the full range. The record gives no primary between-group estimate, confidence interval, or p-value. Consequently, the group summaries can be read as descriptive values, but they do not answer whether a prespecified contrast was statistically supported or how precisely such a contrast was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For continuous outcomes, a group mean is a measure of the average recorded score. A mean difference compares two group averages by subtracting one from the other. Its direction is meaningful only in light of the outcome scale: higher pain-intensity difference is described as better relief, while a higher VAS pain-intensity score means more intensive pain. The recalculated comparisons use the placebo group as the reference and are simple unadjusted comparisons based on posted summary statistics. They are not described as the sponsor's fitted model or as adjusted analyses.

A confidence interval expresses uncertainty around an estimated contrast under the assumptions of the method used. A wider interval indicates less precision than a narrower interval, all else equal. If an interval includes no difference, the data are compatible with no contrast as well as with effects in either direction allowed by the interval. If it excludes no difference, that is evidence against a zero contrast under the corresponding unadjusted analysis, but it does not establish clinical importance or account for other comparisons. The registry does not report a clinically important difference threshold for these outcomes.

The recalculated continuous contrasts use the reported standard errors to derive pooled variability and a standardized effect measure. General explanation: a standard error describes the uncertainty of an estimated mean, whereas a standard deviation describes variation among individual observations. A standard error generally becomes smaller when the estimate is based on more information, but it is not itself a description of participant-to-participant variation. The registry's primary endpoint instead lists dispersion as full range, and the full range can be strongly influenced by extreme observations. It should not be read as a standard error or a confidence interval.

For the binary complete-pain-relief outcome, the risk difference is the difference between the proportion meeting the outcome in the treatment group and the proportion in the placebo group. It is expressed on a probability scale. The recalculated confidence interval indicates uncertainty in that difference, while the unadjusted p-value measures how compatible the observed data are with a zero risk difference under the test assumptions. A p-value is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. The registry posts counts for the groups; the recalculated comparisons use those counts and denominators.

General explanation: over-dispersion matters when observed variation is greater than a statistical model expects. A model that assumes too little variation can produce standard errors that are too small and confidence intervals that are too narrow. The record does not report an over-dispersion assessment or a model for the primary endpoint, so no conclusion about that issue can be made for the sponsor's analysis.

The planning illustrations use an assumed two-sided significance level of 0.05, equal allocation between two groups, and a normal approximation. They consider detecting stated fractions of the observed effect. Such estimates are hypothetical planning aids: they show how sample-size requirements can change with the assumed effect, but do not describe the actual trial design or prove that the study had a particular probability of detecting its observed result. They are not observed power. The registry does not report the trial's own sample-size assumptions or justification.

Multiplicity arises when many outcomes or contrasts are examined. If each is tested without adjustment, the chance of at least one apparently notable result can increase across the family of tests. A multiplicity procedure can control that risk, but the record does not state whether one was planned or used. The posted p-values for secondary comparisons are therefore best treated as unadjusted evidence rather than definitive confirmatory findings. The registry lists no sponsor-reported comparative analyses for the outcomes described in the record.

Finally, a statistical estimate depends on the population and handling of observations used in its calculation. The primary analysis population is specified as randomized participants who received the first dose under staff supervision. The record does not describe missing-data methods, whether all randomized participants contributed to every secondary outcome, or how departures from the planned treatment schedule were handled. Those omissions limit independent assessment of the estimates and the assumptions behind their uncertainty measures.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a prespecified testing hierarchy, or a procedure for controlling multiplicity. This matters because the study includes a primary endpoint, 13 posted secondary outcomes, and multiple treatment groups that could be compared in different ways. When many unadjusted tests are conducted, some results may appear statistically notable by chance. Without a stated family of hypotheses and adjustment method, the secondary p-values cannot be interpreted as multiplicity-controlled confirmatory evidence.

The primary outcome population is described as all randomized participants who received the first dose under study staff supervision. That description is more specific than an analysis of every randomized participant regardless of treatment initiation, but the record does not give a formal name for the analysis population. It does not report the number of participants contributing to each primary or secondary endpoint, reasons for any missing observations, or how missing values were handled. No imputation approach, sensitivity analysis, or missingness assumption is reported.

The endpoint description specifies that a participant's SPID was calculated through the first pre-rescue VAS pain assessment, inclusive, if rescue medication was required. This provides a rule for the endpoint's assessment window in that circumstance. It does not explain the broader treatment-policy question of how rescue medication was incorporated into the treatment effect, whether rescue was analyzed as an outcome, or how observations after rescue were treated for other endpoints.

The record also does not report interim analyses, stopping rules, a primary model, covariate adjustments, or a sample-size justification. These details are not reported in the registry record and should not be inferred from the trial's phase or enrollment. Their absence limits assessment of whether the posted estimates and recalculations correspond to the intended confirmatory analysis. The registry lists no sponsor-reported comparative analyses, so the unadjusted secondary recalculations should not be mistaken for a complete report of the sponsor's analysis.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry records zero serious adverse events in each of the four groups and zero deaths in each group. The number at risk was 75 for Maxigesic IV, 75 for IV acetaminophen, 76 for IV ibuprofen, and 50 for placebo IV. These are recorded counts for the period represented in the registry safety results; they do not establish that serious events could not occur, or that groups are equivalent in safety.

Other adverse events affected 52 participants in the Maxigesic IV group, 45 in the IV acetaminophen group, 58 in the IV ibuprofen group, and 39 in the placebo group. The record does not provide the event terms for those counts in the material available for interpretation, so the counts alone do not describe the nature, severity, timing, or duration of the events. The serious adverse event terms list is empty. A zero count is a report of no events recorded in that category, not proof of absence of risk. The safety counts should be read descriptively and alongside the limited detail in the registry record.

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

The posted data describe a randomized, double-blind, placebo-controlled study of intravenous treatments for acute postoperative pain after bunionectomy. For the primary time-adjusted SPID48 endpoint, Maxigesic IV has the highest reported group mean, followed by IV acetaminophen and IV ibuprofen, with placebo IV lowest. The record also gives broad full ranges for these group summaries. This is a descriptive pattern, not a formal estimate of the primary treatment contrast.

The absence of a posted primary between-group analysis is important. Without that contrast and its uncertainty, the registry summaries do not establish the magnitude or precision of the primary difference between Maxigesic IV and placebo. The secondary recalculations provide some comparative information, but they are unadjusted and arise among many outcomes. They should not be promoted to a substitute primary result or interpreted as a complete confirmatory analysis.

These results do not establish that a treatment works or does not work. Statistical evidence is one component of interpretation; estimates, uncertainty, outcome definition, analysis population, missing-data handling, multiplicity, and clinical context also matter. The registry record does not report a threshold for a clinically important difference, so statistical separation cannot be equated with clinical importance from these data alone.

The safety record shows zero reported serious adverse events and zero deaths in each group, alongside non-serious adverse event counts. These counts are descriptive and do not demonstrate equal safety or rule out uncommon events. The available registry information supports a cautious reading of the recorded outcomes, while leaving important aspects of the planned and conducted statistical analysis unreported.

13. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a posted primary outcome do not, on their own, provide a complete statistical answer. The four-group design offers a framework for comparing a combination treatment with placebo and with its individual components. The registry identifies the primary endpoint and describes how it is constructed, including its handling of pain assessments before rescue medication. Yet the reported primary group summaries are not accompanied by the primary contrast, its uncertainty, or a test result. Readers therefore need to distinguish descriptive group values from evidence about a between-group effect.

The record also demonstrates how secondary results can look more informative than the primary record while still carrying important qualifications. Recalculated differences and p-values can be useful for understanding the posted data, but they are unadjusted and do not reproduce a reported sponsor analysis. With multiple outcomes and possible contrasts, the absence of a stated multiplicity strategy makes isolated secondary findings less secure as confirmatory evidence.

Planning illustrations provide another statistical lesson: sample-size calculations depend on assumptions about the effect to detect, allocation, significance level, and analysis method. The displayed planning estimates are illustrations based on observed effects, not evidence that the trial was designed around those assumptions or that it had observed power. The trial-specific rationale is not reported in the registry record.

Finally, the safety counts show why zero serious events should be read as a recorded count, not as proof of no risk. Across efficacy and safety, careful interpretation depends on complete reporting of analysis populations, uncertainty, missing data, and planned comparisons. This record makes some clinical outcomes visible but leaves those analytical details unresolved.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for interpreting efficacy is that the registry provides no formal primary comparison, confidence interval, or p-value for the primary endpoint. The group means and full ranges are descriptive, and the ranges are not labeled as confidence intervals. Their width and overlap cannot be used as a substitute for a specified treatment-effect analysis.

The primary endpoint uses repeated pain assessments and a time adjustment, with the SPID calculation ending at the first pre-rescue assessment when rescue medication is used. This rule is reported, but the record does not explain the broader estimand for rescue use or provide sensitivity analyses. The record also does not report missing-data methods, endpoint-specific denominators, or whether the specified primary population contributed data to every outcome.

Secondary comparisons are recalculated from posted summary statistics and are unadjusted. They do not include the sponsor's reported model or any stated multiplicity correction. The registry lists 13 posted secondary outcomes but does not provide a complete set of comparative analyses in the record. The possibility that the visible secondary results do not represent the full analysis cannot be resolved from the registry information.

The study has four groups, and the listed group sizes are not equal. The record does not explain the allocation ratio or how the enrollment target was chosen. It does not report details of sequence generation, allocation concealment, masking procedures, adherence, or the timing and duration of safety follow-up. The primary endpoint dispersion is described as full range, which is sensitive to extreme observations and does not directly quantify uncertainty in the mean. These reporting gaps limit assessment of precision, analysis assumptions, and the generalizability of the observed results beyond the recorded bunionectomy setting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Maxigesic IV Phase 3 Bunionectomy Study — NCT02689063.
• Registry record last updated 2021-07-06; status last verified 2016-02.
• Results first posted 2021-07-06.
• 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

NCT02689063 is a completed Phase 3 randomized, double-blind, parallel-group, placebo-controlled study sponsored by AFT Pharmaceuticals, Ltd. It enrolled 276 participants with postoperative pain following bunionectomy and compared Maxigesic IV, IV acetaminophen, IV ibuprofen, and placebo IV. The primary outcome was time-adjusted summed pain-intensity difference 48 hours after the first dose. The registry reports group means and full ranges but no primary between-group analysis.

The record lists 13 secondary outcomes and provides selected group summaries and unadjusted recalculated comparisons. It does not report a statistical analysis plan, multiplicity adjustment, missing-data method, or trial-specific sample-size justification. Serious adverse event and death counts are zero in each group; other adverse event counts are also posted. These safety data are descriptive and do not establish equivalent safety.