A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy (NCT00478023), a randomized phase 3 study. The primary outcome is Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity..

2. Clinical Question

The central statistical question is about average change in reported pain intensity over a defined postoperative interval. The endpoint combines repeated pain ratings into one summary measure; it is not a count of participants who achieved a particular degree of relief. Higher positive values indicate a greater sum of decreases from baseline under the endpoint’s stated calculation, while negative values can represent an increase in pain. The registry describes the theoretical SPID24 range as -240 to 240, under its stated assumptions about baseline and subsequent ratings.

The study record lists 854 participants enrolled and describes a randomized, double-blind, parallel-arm trial in its official title; the masking classification in the record is triple. The outcome estimates concern the listed analysis population, not necessarily every enrolled participant. Results are group averages with substantial within-group variation, so the primary question is best read as a comparison of average outcomes rather than a prediction for any individual participant.

3. Trial Design

The registry record describes a Phase 3 randomized, parallel-arm trial of multiple oral doses of immediate-release CG5503 after abdominal hysterectomy. The official title calls the study double-blind, while the record’s masking classification is triple. The five treatment groups were morphine, CG5503 50 mg, CG5503 75 mg, CG5503 100 mg, and matched placebo. The stated objective was to evaluate efficacy and safety of the three CG5503 doses compared with placebo.

The record lists 854 participants enrolled. The reported primary outcome population is narrower in definition: randomized participants had to receive any amount of study drug and have a non-missing baseline pain assessment, with last observation carried forward used for missing follow-up measurements. The arm summaries for the primary endpoint include 164 participants for morphine, 163 for CG5503 50 mg, 167 for CG5503 75 mg, 172 for CG5503 100 mg, and 166 for placebo. These outcome counts should not be treated as a replacement for the overall enrollment figure; the registry record does not explain the differences between enrollment and the analyzed groups.

The primary outcome timeframe was baseline to 24 hours after first study-drug intake. A secondary outcome used the same general pain-intensity-difference measure over a timeframe ending 48 hours after first intake. The trial status is completed. The record lists a start of 2007-05 and primary completion in 2008-02.

Some design details are not reported in the registry record, including the randomization procedure, the precise roles of masking, the protocol’s allocation ratios, and the original sample-size justification. The number enrolled alone does not establish what effect the study was designed to detect or whether the original assumptions were met. The record also does not report a detailed protocol-based statistical analysis plan in the information available for these results.

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: This trial consisted of 5 periods: a Screening (Day -28 to Day -4 to the Pre-operative Visit) a Surgical (Day -1 to 1), a Postoperative Qualification, a Double-blind Treatment(Day 1-4) and a Follow-up Period (4-14 days after the double-blind treatment). The results refer to randomized subjects.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to Treat (ITT) and Last Observation Carried Forward (LOCF), i.e. all randomized subjects who received any amount of Investigational Medicinal Product (IMP = study drug) and had a non missing baseline pain assessment.

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 Differences Relative to the Baseline Pain Intensity., measured over Baseline to 24 hours after first intake of study drug.

The primary endpoint is the sum of pain-intensity differences relative to baseline over the period from baseline to 24 hours after first intake of study drug. Pain intensity was assessed at predefined time points using an 11-point Numeric Rating Scale, with zero defined as “no pain” and ten as “pain as bad as you can imagine.” At each time point, the difference was calculated as baseline minus the post-baseline score, and those differences were summed to form SPID24.

This construction turns repeated ratings into a single continuous outcome for comparing group averages over the stated interval. Positive values reflect summed decreases from baseline, and a negative value can reflect increased pain under the record’s definition. The registry gives a theoretical range from -240 to 240, assuming a baseline rating of 10 and all subsequent ratings of 0 for the upper end, and an increase in pain for the lower end.

Using the mean allows a direct comparison of average scores across randomized groups, while the standard deviation describes variation among participants. A mean does not show how many individuals experienced a particular outcome, and the registry does not provide a responder threshold or a threshold for clinical importance. The endpoint is specific to the stated rating method, calculation, and 24-hour window; it should not be interpreted as a measure of longer-term pain or function.

7. Results Posted in the Registry

• Morphine: mean 48.80 versus 29.00 on control; difference 19.80 (95% CI 10.52 to 29.08), standardized effect d = 0.46; z-test p = <0.001.
• CG5503 50mg: mean 49.00 versus 29.00 on control; difference 20.00 (95% CI 10.82 to 29.18), standardized effect d = 0.47; z-test p = <0.001.
• CG5503 75mg: mean 52.40 versus 29.00 on control; difference 23.40 (95% CI 14.07 to 32.73), standardized effect d = 0.54; z-test p = <0.001.
• CG5503 100mg: mean 52.90 versus 29.00 on control; difference 23.90 (95% CI 14.72 to 33.08), standardized effect d = 0.56; 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.

Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity

• 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:
  • Morphine: mean 116.60 versus 71.10 on control; difference 45.50 (95% CI 25.14 to 65.86), standardized effect d = 0.48; z-test p = <0.001.
  • CG5503 50mg: mean 112.40 versus 71.10 on control; difference 41.30 (95% CI 20.89 to 61.71), standardized effect d = 0.44; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine 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 CG5503 50mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists one secondary outcome: the sum of pain-intensity differences from baseline through 48 hours after first study-drug intake. The arm-level summaries show a pattern in the same broad direction as the primary endpoint, with higher mean values in the active-treatment groups than in placebo. This is a continuation of the pain-intensity measure over a longer stated observation window, rather than an independent type of outcome.

The available sponsor analyses for this secondary outcome are limited to two placebo comparisons, and the simple recalculations cover the posted morphine and CG5503 50 mg comparisons. The record does not provide sponsor ANCOVA results for every arm in this secondary comparison. The broader pattern can be considered supportive in the descriptive sense that the posted comparisons do not reverse the direction seen for the primary outcome, but it is not a separate confirmation independent of the primary endpoint.

General explanation: Secondary outcomes can help describe whether findings extend to other timeframes or measures. When they are related to the primary outcome, their results may be correlated rather than independent. Testing multiple outcomes and treatment contrasts also creates multiplicity: the more hypotheses considered, the greater the opportunity for a nominally small p-value to occur by chance under a collection of null effects. A prespecified adjustment or hierarchy can address this issue, but such a strategy is not reported in the registry record.

For those reasons, unadjusted secondary results carry less confirmatory weight than a clearly prespecified primary analysis with an explained multiplicity plan. Their interpretation is further limited by incomplete sponsor comparison coverage in the posted record and the absence of a reported threshold for meaningful change. The secondary endpoint adds context about the longer timeframe, but should not be treated as an independent proof of the primary finding.

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

• Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

General explanation: A mean difference subtracts one group’s average outcome from another group’s average outcome. For this endpoint, a positive difference against placebo means the active group’s mean SPID24 is higher than the placebo group’s mean. Because SPID24 sums baseline-minus-follow-up pain ratings, a higher value corresponds to a larger summed decrease under the endpoint’s definition. It does not mean that every participant in that group had a decrease, nor does it describe the distribution of individual responses.

The unadjusted recalculations use the posted group means and standard deviations to estimate differences and uncertainty. They are not the same as the sponsor’s ANCOVA estimates. The former compare summaries without covariate adjustment; ANCOVA is a regression approach that can adjust the group comparison for specified covariates. The registry record does not identify the covariates used in the sponsor’s model, so the source of the numerical difference between estimates cannot be assessed in detail.

What does the standard deviation tell the reader?

General explanation: A standard deviation describes the spread of observed participant values around a group mean. A larger value indicates more variation in the measured outcome within that group. It is not the uncertainty of the mean itself, and it is not a range containing every participant’s result. The primary endpoint standard deviations are substantial in relation to the differences between group averages, underscoring that participants’ scores varied considerably within each treatment group.

The uncertainty of a mean difference depends on both variability and the number of analyzed participants. In the simple recalculations, standard errors for each group mean are derived from the reported standard deviation and analysis count. The difference’s standard error reflects uncertainty in both means. These calculations use group-level summaries and do not reproduce an individual-participant analysis or any adjustment in the sponsor’s model.

How should p-values be read?

General explanation: A p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The recalculated p-values are unadjusted. The sponsor reports p-values from ANCOVA. Since the registry does not report a multiplicity strategy, the p-values should not be treated as adjusted for the set of treatment comparisons.

The reported p-values are small, but the interpretation should be considered alongside the estimated differences, confidence intervals, analysis methods, and limits of the record. A p-value alone does not indicate whether the observed difference meets a clinically meaningful threshold; such a threshold is not reported in the registry record.

What does ANCOVA contribute?

General explanation: Analysis of covariance models an outcome by treatment group while accounting for one or more measured covariates. Depending on the model and chosen covariates, the adjusted estimate can differ from an unadjusted difference of means. ANCOVA can improve precision when appropriate prognostic information is included, but assessment requires knowing the model, covariates, and assumptions. The registry lists ANCOVA as the sponsor’s method and reports least-square mean differences, confidence intervals, and p-values. The model details are not reported in the registry record, so the sponsor’s adjusted estimates can be quoted but not fully reconstructed from the information posted.

Why does the missing-data approach matter?

The primary outcome population is described as intention to treat and last observation carried forward, subject to receiving some study drug and having a non-missing baseline pain assessment. The term intention to treat is used in the record, but the stated eligibility conditions mean that this analysis is not simply all enrolled participants. Last observation carried forward replaces a missing later measurement with the last available observation. General explanation: This approach makes an assumption that the last observed value is a suitable stand-in for later unobserved values. That assumption may not match what would have happened after the measurement stopped, and its consequences depend on why data are missing and when they are missing. The registry does not report the amount, timing, or reasons for missing outcome data, or sensitivity analyses addressing the LOCF assumption.

What does randomization support?

General explanation: Random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. It does not guarantee balance in a particular trial, and evaluating balance requires baseline information. The registry identifies the study as randomized, but the randomization procedure and baseline group details are not reported in the record summarized for these results. The trial is described as parallel-arm, meaning participants were assigned to a group rather than crossing through each treatment condition in sequence.

Masking can reduce the influence of expectations on participant reports, care, or outcome assessment. The record classifies masking as triple, and the official title describes the trial as double-blind. The specific people or roles masked are not reported in the registry record, so the scope of masking cannot be specified further.

11. Confidence Intervals and Precision

The recalculated unadjusted 95% confidence intervals for the primary mean differences are 10.82 to 29.18 for CG5503 50 mg versus placebo, 14.07 to 32.73 for CG5503 75 mg versus placebo, 14.72 to 33.08 for CG5503 100 mg versus placebo, and 10.52 to 29.08 for morphine versus placebo. Each interval lies above zero. The intervals express uncertainty in the estimated average differences under the simple unadjusted calculation; they are not ranges of individual participant outcomes.

General explanation: A confidence interval gives a range of values reasonably compatible with the data and the analysis method at the stated confidence level. A narrower interval indicates greater precision for the estimate, while a wider interval indicates more uncertainty. Interval width is affected by the variability of the endpoint and the number of participants analyzed, as well as by the statistical method. Confidence intervals do not automatically account for missing-data bias, unreported model choices, or multiple comparisons.

The sponsor reports 95% confidence intervals from ANCOVA. Those are distinct from the recalculated intervals because the sponsor’s method reports adjusted least-square mean differences. The sponsor intervals are also above zero for the four listed placebo comparisons, and their reported p-values are < 0.001. The registry does not provide enough detail to reproduce the adjustment or evaluate the model’s assumptions.

Precision should not be confused with clinical importance. The registry record does not report a threshold for a meaningful SPID24 difference, and the confidence intervals address uncertainty in average differences rather than the probability that a particular participant would experience a specific outcome. The sizeable standard deviations show that individual outcomes varied within treatment groups even when the estimated group-average differences were positive.

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 sample-size figures are planning illustrations based on the observed effect, not a reconstruction of the trial’s original design. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The figures are participants per arm for these continuous-outcome comparisons; they are not total event counts.

The 80% power column gives the number of participants per arm estimated to provide an 80% chance of detecting the specified effect under those assumptions, if that effect and the other assumptions were correct. The 90% power column gives the corresponding number per arm for a 90% chance. These are planning concepts, not guarantees of a result. The original sample-size justification and assumptions are not reported in the registry record.

Each planning row scales the effect to be detected relative to the observed estimate: the full observed effect, 75% of it, or 50% of it. Smaller target effects require more participants because a smaller difference is harder to distinguish from random variation at a given level of variability. This relationship is visible across the planning entries for each comparison. The values are illustrative and depend on the observed effect and the stated simplified assumptions; they do not establish what effect the actual trial was planned to detect.

This is not observed power. Observed power calculated from an effect estimate and its uncertainty would not add a useful interpretation beyond the estimate and confidence interval. The planning figures are best read as conditional estimates for future-study planning, not as a retrospective score of whether the completed trial succeeded.

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 = 19.800; pooled standard deviation σ = 43.048.
2. n = 2 × (1.96 + 0.842)² × 43.048² / 19.800² = 74.2, rounded up to 75 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 <- 19.8                      # observed difference in means
sigma <- 43.0481531996721                     # 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(478023)
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 = 75 (80% power), 100 (90% power)
 75% of observed effect: n per arm = 132 (80% power), 177 (90% power)
 50% of observed effect: n per arm = 297 (80% power), 398 (90% power)
power.t.test: 75.2 
Simulated power at n = 75 per arm: 0.796 (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 the sponsor’s primary analyses as ANCOVA comparisons of each active group with placebo, using least-square mean differences. For CG5503 50 mg, 75 mg, and 100 mg, and for morphine, the reported adjusted estimates are positive; each reported 95% confidence interval is above zero, and each p-value is < 0.001. Those are the sponsor’s own reported analyses.

The recalculated comparisons are simple, unadjusted differences between the posted group means. They also produce positive estimates, intervals above zero, and p-values of <0.001 for the same active-group comparisons. The numerical estimates differ from the sponsor’s adjusted estimates, which is expected when a covariate-adjusted analysis is compared with a calculation based only on group means and standard deviations. The registry record does not state the ANCOVA covariates or full model details, so the adjusted estimates cannot be rebuilt from the posted summaries alone.

The record’s discrepancy indicator is false, so there is no flagged conflict requiring the simple recalculation to take precedence. The sponsor’s analyses remain the reported trial analyses; the recalculations offer a separate, transparent summary-based check, not a replacement for the sponsor’s model. Neither set of comparisons establishes a clinical-importance threshold, which is not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports several treatment comparisons for the primary outcome and a further set of secondary analyses. The sponsor’s reported primary ANCOVA results include comparisons of each active group, including morphine, against placebo. The record does not report a multiplicity procedure, such as an adjustment across dose groups, a testing hierarchy, or a prespecified allocation of the type I error rate. The recalculated p-values are explicitly unadjusted; the record does not establish whether the sponsor used a broader multiplicity strategy beyond the individual reported analyses.

General explanation: When several hypotheses are tested, the chance of at least one false-positive result can increase if each is judged using the same unadjusted threshold. Multiplicity procedures control or structure that risk, but they may affect the inferential status of individual comparisons. Without a reported plan, the individual p-values can be read as nominal evidence, while the confidence intervals are not necessarily simultaneous intervals covering the full set of comparisons.

The stated primary outcome population combines an intention-to-treat label with eligibility conditions: participants had to be randomized, receive some study drug, and have a non-missing baseline pain assessment. The method also used last observation carried forward. The record does not report the number of missing values for each time point, when measurements became unavailable, reasons for missingness, or analyses using alternative assumptions. Consequently, the sensitivity of the estimates to missing-data handling cannot be assessed from this record.

The original sample-size justification, planned effect, and trial-specific power assumptions are not reported in the registry record. The planning illustrations based on observed effects are not evidence of the original design rationale. Other details relevant to interpretation—including the complete statistical analysis plan, covariates in the ANCOVA, and the precise prespecification status of the reported analyses—are also not reported. These omissions do not invalidate the posted results, but they limit independent evaluation of whether the analyses followed a fully specified plan and how robust the conclusions are to analytic choices.

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: bronchopneumonia (0.6%), post procedural haemorrhage (0.6%), pulmonary embolism (0.6%), sinus tachycardia (0.6%), confusional state (0.6%).

The registry reports serious adverse events by group as counts among participants at risk. The reported counts were 3 of 170 for morphine, 0 of 168 for CG5503 50 mg, 0 of 171 for CG5503 75 mg, 1 of 176 for CG5503 100 mg, and 0 of 169 for placebo. The record also lists bronchopneumonia, post procedural haemorrhage, pulmonary embolism, sinus tachycardia, and confusional state among the top serious-event terms, each at 0.6%.

These are descriptive safety counts. They do not establish that a treatment caused or prevented an event, and they are not adjusted comparisons between groups. Small counts make estimates uncertain, while the registry summary does not provide event-level timing, exposure duration, severity details beyond the serious-event classification, or causal assessments. The number at risk differs by group and should be retained when reading the reported counts.

The record also reports counts of participants with other adverse events: 99 of 170 for morphine, 84 of 168 for CG5503 50 mg, 96 of 171 for CG5503 75 mg, 106 of 176 for CG5503 100 mg, and 88 of 169 for placebo. Death counts are not reported in the registry record. These summaries should be interpreted as reported safety observations, not as comparative proof of safety or a complete account of benefit and risk.

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

The posted results show higher average SPID24 values in the three CG5503 dose groups and the morphine group than in the placebo group. Both the summary-based recalculations and the sponsor’s reported ANCOVA estimates are positive for the listed comparisons. The confidence intervals for those comparisons lie above zero, and the reported p-values are small. Statistically, these findings indicate evidence of differences in group-average pain-intensity-difference scores over the specified postoperative timeframe under the respective analyses.

That conclusion is narrower than saying how any one participant would fare. Group means conceal the range of individual outcomes, and the standard deviations show substantial within-group variation. The endpoint summarizes repeated ratings rather than reporting the number of participants who reached a specific response threshold. The registry does not report a threshold for clinical importance, so the statistical separation cannot be translated into a judgment about the importance of the magnitude for participants.

The evidence is limited to the defined setting, measure, analysis population, and follow-up windows in the record: women undergoing abdominal hysterectomy, pain-intensity scores summarized through 24 hours for the primary outcome, and through 48 hours for the secondary outcome. The registry record does not report longer-term outcomes, detailed model specification, multiplicity handling, or sensitivity analyses for missing data. Those omissions constrain how broadly the findings can be interpreted.

The safety summaries describe observed adverse events but do not establish causal relationships or provide a complete comparative assessment. The serious-event counts are small, and deaths are not reported in the registry record. Taken together, the posted data support a statistical comparison of group averages in this trial; they do not, by themselves, establish individual outcomes, clinical importance, longer-term effects, or a comprehensive safety profile.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation benefits from distinguishing a group mean from an individual response. The primary endpoint combines repeated pain ratings into a continuous summary, allowing comparisons of average scores, but the means sit alongside substantial variation within groups. A statistically clear difference in averages does not imply that all participants had similar experiences or that the size of the difference has a known clinical meaning.

It also demonstrates the importance of distinguishing adjusted sponsor analyses from simple recalculations. Both approaches point in the same direction in the posted comparisons, but they estimate effects differently. The sponsor’s ANCOVA reports least-square mean differences, whereas the recalculated estimates are unadjusted differences derived from group summaries. A reader should not conflate these numbers or infer model details that the registry does not report.

Several features determine how much confidence can be placed in the inferential claims: an explicit analysis population, handling of missing observations, the full covariate model, and the treatment of multiple comparisons. The registry reports LOCF and an ITT label with stated eligibility criteria, but does not report the missing-data patterns, detailed ANCOVA specification, or multiplicity plan. These are not technical footnotes; they affect how an analyst evaluates robustness and the status of p-values and confidence intervals across several comparisons.

Finally, planning calculations based on observed effects are distinct from original design justification and from observed power. The distinction prevents retrospective planning illustrations from being mistaken for evidence about the trial’s design or the certainty of its findings. Together, these points make the record useful for understanding the reported statistical pattern while keeping its limits in view.

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 leaves several trial-specific questions unresolved. It does not report the method used to generate or conceal the random sequence, the exact people masked, or baseline characteristics by group. Although the study is described as randomized and the masking classification is triple, those details would help readers assess the conduct and comparability of the groups.

The primary analysis population is described with both an intention-to-treat label and conditions requiring receipt of study drug and a non-missing baseline assessment. The record does not state how many enrolled participants were excluded from this outcome analysis or why. It reports LOCF, but not the amount or pattern of missing follow-up data, the reasons for missingness, or sensitivity analyses using alternative methods. Therefore, the possible influence of missing outcomes cannot be evaluated fully.

The registry gives the sponsor’s ANCOVA results but does not report the model covariates, diagnostic checks, or a detailed analysis plan. It also does not state how multiplicity across dose comparisons and outcomes was addressed. The original sample-size rationale is not reported; observed-effect planning calculations cannot fill that gap.

The primary endpoint covers baseline through 24 hours, with a related secondary measure through 48 hours. No longer-term outcomes are reported in the record. The record also does not give a clinical-importance threshold for SPID24, so the practical meaning of the estimated differences cannot be determined from statistical results alone. Safety information is summarized as counts, with death counts not reported in the registry record and limited detail on event timing or attribution. These limitations are specific to what is reported and should not be read as proof that the unreported procedures or analyses were not undertaken.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy — NCT00478023.
• Registry record last updated 2019-10-28; status last verified 2019-10.
• Results first posted 2010-01-27.
• 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

The registry record describes a completed Phase 3 randomized, triple-masked, parallel-arm trial with 854 participants enrolled. It compared morphine, three immediate-release CG5503 doses, and matched placebo after abdominal hysterectomy. The primary endpoint was the sum of pain-intensity differences from baseline through 24 hours after first study-drug intake, analyzed in the stated ITT/LOCF population.

All four posted active-versus-placebo primary comparisons had positive estimates. The sponsor reported ANCOVA results with 95% confidence intervals above zero and p-values of < 0.001; simple unadjusted recalculations likewise had intervals above zero and p-values of <0.001. The record also reports one related 48-hour secondary outcome and adverse-event counts.

Important interpretive details—including the multiplicity plan, missing-data patterns, original sample-size rationale, and full ANCOVA specification—are not reported in the registry record. Clinical importance and individual outcomes cannot be inferred from the group-average results alone.