A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy. (NCT00613938), a randomized phase 3 study. The primary outcome is Sum of Pain Intensity Difference Over 48 Hours (SPID48).

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, quadruple-masked, parallel-group, multicenter study of tapentadol immediate-release formulation for acute pain after bunionectomy. The registry describes it as active- and placebo-controlled. Its listed enrollment was 901, and its status is completed. The recorded study start was 2008-02, with primary completion in 2008-10.

The four treatment groups were placebo, tapentadol 50mg, tapentadol 75mg, and oxycodone 10mg. The arm descriptions specify capsule dosing every 4–6 hours for 3 days. The posted primary endpoint results report an analysis group of 69 for placebo, 275 for tapentadol 50mg, 278 for tapentadol 75mg, and 278 for oxycodone 10mg. These endpoint-specific group sizes should not be conflated with the overall enrollment figure.

Randomization and the parallel-group structure support comparisons of outcomes between assigned groups. Masking can reduce the influence of expectations on outcome assessment, although the registry does not identify which roles were covered by quadruple masking. The protocol’s allocation procedures, detailed masking procedures, and original sample-size justification are not reported in the registry record.

The primary analysis set is described as the Intent to Treat (ITT) analysis set, defined for this endpoint as randomized participants who received at least one dose of study drug and had a non-missing baseline pain-intensity score. This definition is narrower than all randomized participants because it includes the stated treatment and baseline-data conditions. Further details about handling missing follow-up measurements are not reported in the registry record.

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: The study consisted of a screening period (duration up to 28 days), and a double blind active treatment period (4 days).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

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 Sum of Pain Intensity Difference Over 48 Hours (SPID48), measured over 48 hours.

The primary endpoint was the sum of pain-intensity differences over 48 hours, abbreviated SPID48. It combines pain-intensity information across the period rather than representing pain at a single assessment. The registry describes the measure as incorporating the cumulative analgesic effects of tapentadol immediate-release treatment and allowing evaluation across multiple doses even when dosing frequency varies.

Pain intensity was derived from the Numerical Rating Scale, described in the record as ranging from 0 = No pain to 11 = Pain as bad as you can imagine. The endpoint is reported as a mean with standard deviation. The registry states that a higher SPID indicates greater pain relief and that a positive difference between an active-treatment mean and placebo would indicate a numerically larger analgesic effect in the active group.

A cumulative endpoint can be useful when the question concerns the course of pain over a treatment period, rather than a single moment. It summarizes the repeated pain-intensity information in a form that permits group-level comparison. That summary does not, by itself, show the timing of changes, individual responses, or whether the observed difference is important to patients. The registry’s primary analysis population required a non-missing baseline pain-intensity score and at least one dose after randomization.

7. Results Posted in the Registry

• Tapentadol 50mg Fixed Dose: mean 122.20 versus 54.10 on control; difference 68.10 (95% CI 40.56 to 95.64), standardized effect d = 0.68; z-test p = <0.001.
• Tapentadol 75mg Fixed Dose: mean 143.70 versus 54.10 on control; difference 89.60 (95% CI 62.19 to 117.01), standardized effect d = 0.91; z-test p = <0.001.
• Oxycodone 10mg Fixed Dose: mean 140.30 versus 54.10 on control; difference 86.20 (95% CI 58.64 to 113.76), standardized effect d = 0.86; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The SPID at 12 Hours Relative to First Dose.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tapentadol 50mg Fixed Dose: mean 21.10 versus 7.50 on control; difference 13.60 (95% CI 8.07 to 19.13), standardized effect d = 0.63; z-test p = <0.001.
  • Tapentadol 75mg Fixed Dose: mean 26.00 versus 7.50 on control; difference 18.50 (95% CI 12.91 to 24.09), standardized effect d = 0.82; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Tapentadol 50mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Tapentadol 75mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

SPID at 24 Hours Relative to First Dose

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tapentadol 50mg Fixed Dose: mean 45.40 versus 12.10 on control; difference 33.30 (95% CI 21.67 to 44.93), standardized effect d = 0.73; z-test p = <0.001.
  • Tapentadol 75mg Fixed Dose: mean 58.10 versus 12.10 on control; difference 46.00 (95% CI 34.38 to 57.62), standardized effect d = 1.01; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Tapentadol 50mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Tapentadol 75mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change to Day 3

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tapentadol 50mg Fixed Dose: 83.3% (229/275) versus 65.2% (45/69) on control; risk difference 18.1 percentage points (95% CI 6.0 to 30.1), risk ratio 1.28 (1.07–1.53); unadjusted two-proportion z-test p = <0.001.
  • Tapentadol 75mg Fixed Dose: 87.8% (244/278) versus 65.2% (45/69) on control; risk difference 22.6 percentage points (95% CI 10.7 to 34.4), risk ratio 1.35 (1.13–1.61); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Tapentadol 50mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Tapentadol 75mg Fixed Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes point in a direction broadly consistent with the primary endpoint: the reported tapentadol groups have higher mean SPID values than placebo at the earlier pain-intensity time points, and higher reported proportions of participants categorized as much or very much improved by Day 3. The secondary outcomes therefore provide related descriptive context for the primary SPID48 result, rather than an independent replacement for it.

The registry lists time to first rescue pain medication use and total pain relief at 48 hours among its secondary outcomes, but their numerical results are not reported in the registry record. Numerical posted results are available for the SPID measures at 12 and 24 hours and for the Day 3 global-improvement measure. The comparison results included with those outcomes are unadjusted recalculations; the registry does not report sponsor analyses for these listed comparisons.

Secondary outcomes answer different questions and may use different scales or summaries. Agreement in direction can add coherence to the overall pattern, but it does not resolve limitations in the primary analysis or establish clinical importance. A global-improvement rating, a cumulative pain score, and time to rescue medication use are not interchangeable outcomes.

Unadjusted secondary results carry less inferential weight when multiple outcomes and comparisons are examined. Without a reported multiplicity strategy, the chance of at least one apparently notable result across a collection of tests is not accounted for by each individual unadjusted p-value. The registry record does not report how secondary endpoints were prioritized, whether they were confirmatory, or whether any adjustment was used. They are best treated as supportive descriptive evidence, with appropriate caution about multiple testing and incomplete reporting.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to First Rescue Pain Medication Use.
• The SPID at 12 Hours Relative to First Dose.
• SPID at 24 Hours Relative to First Dose
• Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change to Day 3
• Total Pain Relief (TOTPAR)at 48 Hours

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a numeric score summarized by its mean and standard deviation. The posted recalculations estimate the difference between each active group’s mean and the placebo mean. A positive mean difference in these comparisons corresponds to a higher SPID48 mean in the active group, consistent with the endpoint description that higher SPID indicates greater pain relief.

What does the mean difference express?

A mean difference is an absolute contrast on the endpoint’s scale. It keeps the comparison tied to the SPID48 units, unlike a standardized effect size, which expresses the difference relative to variability. The recalculations use the posted group means and standard deviations to estimate these contrasts. They are described as simple, unadjusted recalculations, not as the sponsor’s adjusted analysis.

The recalculated mean differences are 68.1 for tapentadol 50mg versus placebo, 89.6 for tapentadol 75mg versus placebo, and 86.2 for oxycodone 10mg versus placebo. The corresponding confidence intervals and unadjusted p-values are reported with each comparison. These estimates do not compare tapentadol directly with oxycodone or compare the two tapentadol doses with each other.

Why are standard deviations relevant?

A standard deviation describes how spread out individual observations are around a group mean. It is not the uncertainty interval for the mean and does not indicate the range of all observations. When participant outcomes vary widely, the mean alone gives an incomplete picture of the group’s results. Here, the posted standard deviations describe substantial within-group variation in SPID48.

The standard error concerns uncertainty in an estimated mean or contrast, rather than the spread of individual outcomes. A confidence interval is formed around an estimate using its uncertainty. In general, more precise estimates have narrower intervals, while greater variability or less information can make intervals wider. These are general statistical principles; the registry does not report all details of the recalculation procedure.

What does the p-value say?

A p-value assesses how compatible the observed data are with a specified null hypothesis under the statistical model. The unadjusted p-values of <0.001 indicate that the recalculated differences would be unusual under a null hypothesis of no mean difference, given the assumptions of that analysis. A p-value does not measure the probability that the null hypothesis is true, the size or importance of the effect, or the chance that a result will replicate.

Because these p-values are unadjusted, they do not account for the fact that multiple treatment comparisons and outcomes are considered. The registry record does not report the multiplicity procedure used for the sponsor’s broader analysis, if any. Consequently, the posted unadjusted values should not be treated as if they were adjusted for the full set of analyses.

How does the sponsor analysis differ?

The registry reports an ANCOVA analysis across the four groups, with a mean difference (final values) of 62.4, a 95% confidence interval from 39.01 to 85.73, and p <0.001. ANCOVA is a general method for comparing outcomes while accounting for specified covariates. The covariates and model details for this reported result are not reported in the registry record. Its stated result is not identical in description to the unadjusted recalculated pairwise mean differences, so the figures should not be substituted for one another.

What can the analysis set tell us?

The primary analysis set includes randomized participants who received at least one dose and had a non-missing baseline pain-intensity score. This definition identifies who contributed under the registry’s stated primary analysis population. It does not explain how missing post-baseline outcomes were handled, whether imputation was used, or how participants with incomplete follow-up were treated. Those details are not reported in the registry record.

All such methods shape the interpretation of a trial estimate. Randomization supports treatment-group comparability, but the analysis population, missing-data approach, outcome measurement, and model assumptions also matter. Statistical evidence of a difference does not alone determine its clinical significance or applicability beyond the population and setting studied.

11. Confidence Intervals and Precision

The 95% confidence intervals for the recalculated SPID48 mean differences are 40.56 to 95.64 for tapentadol 50mg versus placebo, 62.19 to 117.0 for tapentadol 75mg versus placebo, and 58.64 to 113.8 for oxycodone 10mg versus placebo. Each interval lies above zero, aligning with the reported unadjusted p-value of <0.001 for each comparison. The intervals describe uncertainty in the estimated mean differences under the recalculation’s assumptions; they do not describe the spread of individual outcomes.

The intervals also show that the exact size of each mean difference is uncertain. Their width reflects the precision of the corresponding estimate, and the ranges overlap across comparisons. Overlap is not a formal test of whether treatment groups differ from each other. In particular, these placebo-referenced intervals do not establish a difference between either tapentadol dose and oxycodone, or between the tapentadol doses.

The trial reports standard deviations for each group but does not report confidence intervals for the individual group means. The reported ANCOVA estimate has a 95% confidence interval from 39.01 to 85.73, but the registry’s description does not specify a direct treatment contrast for that estimate. The recalculated intervals and the ANCOVA interval therefore refer to analyses with different descriptions and should be interpreted in that context.

Precision is not the same as importance. A confidence interval can help show which effect sizes are compatible with the data under a model, but it does not determine whether those values matter to patients. A threshold for a clinically important SPID48 difference is not reported in the registry record. The posted summaries also do not show individual outcome distributions or how sensitive the estimates are to alternative missing-data assumptions.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effects, not the trial’s original design calculations. For these continuous-outcome comparisons, the displayed figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers detecting the stated fraction of the observed effect.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and assumptions hold. The 90% power column gives the corresponding per-arm figure for a design with a 90% chance. These are planning targets, not evidence that the completed trial had a particular probability of detecting an effect.

Rows that plan for 75% or 50% of the observed effect use a smaller target effect than the row based on 100% of the observed effect. Smaller effects are harder to distinguish from random variation and therefore require more participants under otherwise comparable assumptions. The figures are sensitive to assumptions about effect size, variability, allocation, and the analysis.

This is not observed power. The trial’s own original sample-size assumptions and justification are not reported in the registry record, so the planning illustrations should not be read as a reconstruction of the trial’s design or as a measure of its achieved power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 68.100; pooled standard deviation σ = 100.108.
2. n = 2 × (1.96 + 0.842)² × 100.108² / 68.100² = 33.9, rounded up to 34 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 68.1                      # observed difference in means
sigma <- 100.107609224081                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(613938)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 34 (80% power), 46 (90% power)
 75% of observed effect: n per arm = 61 (80% power), 81 (90% power)
 50% of observed effect: n per arm = 136 (80% power), 182 (90% power)
power.t.test: 34.9 
Simulated power at n = 34 per arm: 0.789 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using ANCOVA across the four groups. Its reported result is a mean difference (final values) of 62.4, with a 95% confidence interval from 39.01 to 85.73 and p <0.001. The registry does not specify the covariates or provide enough detail in this result description to identify it as a particular pairwise contrast.

The unadjusted recalculations instead give separate active-treatment-versus-placebo mean differences: 68.1 for tapentadol 50mg, 89.6 for tapentadol 75mg, and 86.2 for oxycodone 10mg. They are based on posted group summaries and are not the same analysis as the sponsor’s ANCOVA. Differences in estimand or model can produce estimates that are not directly interchangeable.

The registry marks no discrepancy between the posted results and the recalculations. The sponsor’s result should therefore be read as the trial’s reported ANCOVA analysis, while the pairwise recalculations provide unadjusted contrasts based on the group summaries. Neither description supports assigning the ANCOVA estimate to a specific treatment comparison without further model details. Those details are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The study includes a primary endpoint, several secondary outcomes, and comparisons among multiple treatment groups. This creates a multiplicity issue: as more hypotheses are tested, interpreting each unadjusted result as if it were the only test can overstate the strength of evidence. The recalculated p-values are explicitly unadjusted. A multiplicity adjustment or testing hierarchy for the sponsor’s analyses is not reported in the registry record.

The registry reports one ANCOVA analysis across the four groups for the primary endpoint and lists secondary outcomes, but it does not describe a prespecified sequence for testing them or state which secondary comparisons were confirmatory. The original statistical analysis plan, including any interim analyses, is not reported in the registry record. No interim-analysis procedure should be inferred from the posted results.

The primary analysis population is described as randomized participants who received at least one dose and had a non-missing baseline pain-intensity score. This provides an explicit definition for the reported primary analysis set, but does not fully describe how missing outcome measurements after baseline were handled. The imputation method, reasons for missingness, and sensitivity analyses are not reported in the registry record.

Missing-data handling matters because the observed outcomes may not represent all randomized participants if follow-up data are incomplete. Statistical methods can address missingness only under assumptions, and different assumptions can affect estimates. The record does not provide enough information to assess the robustness of the primary result to alternative missing-data approaches.

These reporting gaps do not negate the posted estimates, but they limit independent assessment of the full analysis strategy. Readers can distinguish the reported ANCOVA result from the unadjusted recalculations and interpret secondary results as less definitive when adjustment and testing priorities are not documented.

16. 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: deep vein thrombosis (0.4%).

The serious adverse event summary reports zero affected participants in placebo, tapentadol 50mg, and tapentadol 75mg groups, and one affected participant in the oxycodone 10mg group. The corresponding numbers at risk are 69, 275, 278, and 279. These figures describe the registry’s serious-event summary; they do not identify the total burden or duration of all adverse events.

Deep vein thrombosis is listed among the top serious-event terms at 0.4%. The record does not link that term to a specific treatment group in the posted summary. Death counts are not reported in the registry record.

Other adverse events were reported for 25 participants in the placebo group, 161 in the tapentadol 50mg group, 192 in the tapentadol 75mg group, and 218 in the oxycodone 10mg group, with the listed at-risk group sizes as above. These other-event counts are distinct from serious adverse events and should not be treated as counts of serious events. The registry summary does not provide enough detail to assess event severity, duration, or causal attribution. These counts alone do not establish comparative safety.

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

The posted primary results show higher mean SPID48 in each active-treatment group than in placebo, with unadjusted recalculated mean differences whose 95% confidence intervals lie above zero. The endpoint’s stated direction means higher SPID corresponds to greater pain relief. The sponsor-reported ANCOVA result also has p <0.001, but its result description does not identify a specific pairwise treatment contrast.

These findings describe average outcomes in the trial’s bunionectomy population over the stated treatment period. They do not mean every participant experienced the group-average outcome, and they do not establish that the treatments differ from one another. The posted pairwise recalculations compare each active group with placebo; they are not head-to-head tests between active groups.

Statistical evidence against a no-difference hypothesis is not the same as evidence that a difference is important to patients. The registry record does not report a threshold for clinical importance on SPID48. Nor do these aggregate results establish the balance of benefits and harms for an individual or support treatment advice.

The conclusions are limited to the population, setting, doses, and treatment schedule described in the record. The results do not establish how outcomes would compare in other surgical settings, other populations, or with other dosing regimens. Incomplete information about missing-data handling, multiplicity, and the details of the sponsor’s ANCOVA also limits how fully the statistical analysis can be independently evaluated.

The secondary findings are generally directionally consistent with the primary pattern, but multiple unadjusted outcomes are less conclusive than a prespecified and fully documented analysis strategy. Some listed secondary outcomes lack numerical results in the registry record. Overall, the posted evidence supports a between-group difference in the primary endpoint versus placebo under the reported analyses, while leaving questions about clinical importance, active-treatment contrasts, and broader applicability unresolved.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of endpoint matters. SPID48 compresses repeated pain-intensity information over an extended treatment period into a cumulative measure, which can represent more than a single assessment. It also illustrates a trade-off: a summary score can be useful for group comparisons while obscuring the timing and distribution of individual responses.

It is also a useful example of separating an estimate from its precision and its interpretation. The mean differences, confidence intervals, and p-values answer related but distinct questions. The p-values indicate evidence against a null hypothesis under the unadjusted analysis; the confidence intervals describe uncertainty in effect size; neither determines whether the difference is clinically important.

The record juxtaposes a sponsor-reported ANCOVA result with recalculated unadjusted comparisons. These analyses are not interchangeable simply because they concern the same endpoint. Clear reporting of the estimand, model, covariates, analysis population, and multiplicity strategy helps readers understand what each estimate means and how it should be compared with other results.

Finally, planning illustrations based on an observed effect should be kept separate from the trial’s original design assumptions and from observed power. They show how planning requirements change when the target effect changes under stated assumptions; they do not reveal why this trial enrolled its participants or establish the probability that it detected its result.

19. 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 registry record does not report the original sample-size justification or design assumptions. The posted planning figures are illustrations based on the observed effect and cannot explain the trial’s enrollment target. The detailed randomization procedures and the roles covered by quadruple masking are also not reported in the registry record.

For the primary outcome, the registry defines the ITT analysis set using randomization, receipt of at least one dose, and a non-missing baseline score. It does not describe handling of missing post-baseline outcomes, report sensitivity analyses, or provide enough information to evaluate the impact of incomplete follow-up. The posted group means and standard deviations also do not reveal individual response patterns.

The sponsor’s ANCOVA result is reported across the four groups, but the covariates, model specification, and specific contrast represented by the reported mean difference are not stated. The pairwise recalculations are unadjusted, and the registry does not report a multiplicity procedure or hierarchy for primary and secondary tests. These omissions limit comparison among analyses and interpretation of the family of p-values.

The registry lists secondary outcomes for time to first rescue pain medication use and total pain relief at 48 hours, but their numerical results are not reported in the registry record. For the safety summary, deaths are not reported, and the serious-event term listed is not linked to a particular group in the summary. The record also does not provide a clinical-importance threshold for SPID48. These limitations constrain interpretation without changing the meaning of the estimates that are posted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy. — NCT00613938.
• Registry record last updated 2014-05-09; status last verified 2014-04.
• Results first posted 2010-04-23.
• 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.

23. Record Summary

This completed randomized, quadruple-masked, parallel-group phase 3 study evaluated tapentadol immediate-release treatment for acute pain after bunionectomy, with oxycodone and placebo as comparators. The primary endpoint was SPID48, a cumulative pain-intensity measure for which higher values indicate greater pain relief.

Posted group means were higher for both tapentadol groups and oxycodone than for placebo. Unadjusted recalculations found mean differences versus placebo with 95% confidence intervals above zero and p-values of <0.001. The registry also reports an ANCOVA result across the four groups. These results should be distinguished because the sponsor analysis and the pairwise recalculations are not described as the same contrast.

Secondary outcomes show a broadly consistent direction where numerical results are posted, but some listed secondary results are not reported, and multiplicity handling is not documented. Missing-data procedures and the original sample-size rationale are also not reported in the registry record. The estimates describe this trial and do not by themselves establish clinical importance, active-treatment differences, or broader applicability.