Transversus Abdominis Plane Block in Microsurgical Breast Recon w/Abdominal Free Flap in Breast CA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transversus Abdominis Plane Block in Microsurgical Breast Recon w/Abdominal Free Flap in Breast CA (NCT02601027), a randomized phase 3 study. The primary outcome is Post-operative Narcotic Usage.

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, double-blind, parallel-group study sponsored by Stanford University. The registry record lists enrollment of 120 and describes patients undergoing abdominal free flap-based breast reconstruction. The study began in 2015-11, had a primary completion date of 2019-09-07, and is marked completed. These registry entries establish the broad design and timing, but do not describe the allocation procedure, masking procedures, or participant flow in detail.

The two groups received different infusions through TAP catheters: 0.125% bupivacaine in the intervention group and saline in the placebo group. The primary outcome was post-operative narcotic usage over 48 hours, expressed as OME. The posted primary outcome summaries include 44 participants in the bupivacaine group and 46 in the placebo group. Those outcome denominators do not match the registry’s overall enrollment figure; the record does not explain the difference. The adverse-event groups have separate denominators, also described in the safety discussion.

The registry lists post-operative pain score, anti-emetic usage, time to ambulation, time to first bowel movement, and quality of life measurement as secondary outcomes. Numeric results are available for pain score, anti-emetic usage, and time to ambulation. Numeric findings for time to first bowel movement and quality of life measurement are not reported in the registry record. The record also does not report the trial’s original sample-size justification, detailed statistical analysis plan, analysis populations, or handling of missing outcomes.

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.

Registration to Surgery

Reasons for not completing this period:

Surgery to Assessments

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 Post-operative Narcotic Usage, measured over 48 hours.

The primary endpoint is post-operative narcotic usage during the first 48 hours after breast reconstruction. Narcotic type and amount were converted to the oral morphine equivalent (OME) amount that would be orally administered to achieve the same event. This conversion places different narcotics on a common scale for summarizing use. The outcome is reported as a mean and standard deviation for each group.

This endpoint addresses the study’s stated question about whether a pre-operative TAP block followed by continued local anesthetic infusion affects post-operative narcotic use, compared with a placebo TAP block. A continuous measure such as OME can capture variation in the amount used across participants, while the group mean provides a summary for comparing average use. In general, a mean alone does not show how widely individual observations vary; the standard deviation helps describe that spread. The registry record does not report additional details about how missing OME measurements, rescue medication, or individual narcotic records were handled.

The posted means are 139.3 mg for bupivacaine and 169.2 mg for placebo. The recalculated unadjusted mean difference, defined as bupivacaine minus placebo, is -29.9 mg. This is a description of the posted summaries and does not by itself establish the precision or certainty of the difference; the confidence interval is important for that assessment.

7. Results Posted in the Registry

• 0.125% Bupivacaine: mean 139.30 versus 169.20 on control; difference -29.90 (95% CI -82.39 to 22.59), standardized effect d = -0.23; z-test p = 0.264.

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.

Post-operative Pain Score

• 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:
  • 0.125% Bupivacaine: mean 3.76 versus 3.96 on control; difference -0.20 (95% CI -1.00 to 0.60), standardized effect d = -0.10; z-test p = 0.624.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 0.125% Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

Post-operative Anti-emetic Usage

• 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:
  • 0.125% Bupivacaine: mean 5.14 versus 9.93 on control; difference -4.79 (95% CI -9.06 to -0.52), standardized effect d = -0.46; z-test p = 0.028.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 0.125% Bupivacaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Ambulation

• 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:
  • 0.125% Bupivacaine: mean 1.28 versus 1.45 on control; difference -0.17 (95% CI -0.41 to 0.07), standardized effect d = -0.30; z-test p = 0.158.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 0.125% Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

The posted numerical summaries for the secondary outcomes show a consistent direction in their group means: the bupivacaine group mean is lower than the placebo group mean for post-operative pain score, anti-emetic usage, and time to ambulation. The uncertainty differs across these comparisons. The unadjusted comparisons for pain score and time to ambulation do not provide clear evidence of a group difference, while the anti-emetic comparison has an unadjusted p-value of 0.028 and a confidence interval that does not include zero.

That secondary pattern does not replace the primary result. The primary outcome concerns OME use and its confidence interval includes zero. Secondary outcomes address related but distinct aspects of post-operative recovery, so a directional pattern across them is not equivalent to a confirmed effect on narcotic usage. The registry also lists time to first bowel movement and quality of life measurement, but numerical findings for those outcomes are not reported in the registry record.

Unadjusted secondary findings carry less weight for confirmatory interpretation when the record does not state how many comparisons were planned, which outcomes were considered confirmatory, or whether a multiplicity strategy was used. In general, considering many outcomes creates more opportunities for an apparently notable result to occur by chance. The record contains no reported secondary analyses or multiplicity plan to clarify how the anti-emetic result should be framed. It is therefore best treated as an exploratory signal within a set of outcomes, rather than as a stand-alone conclusion.

The secondary results can still be useful descriptively. They show the recorded group means and indicate where uncertainty remains, but they do not establish a unified effect across recovery outcomes. The outcomes also use different measures and timeframes, so their estimates should not be pooled or treated as interchangeable based on this record.

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

• Post-operative Pain Score
• Post-operative Anti-emetic Usage
• Time to Ambulation
• Time to First Bowel Movement
• Quality of Life Measurement

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it records OME use on a numeric scale and is summarized by a mean and standard deviation. The bupivacaine group mean is 139.3 mg with a standard deviation of 117.2 mg; the placebo group mean is 169.2 mg with a standard deviation of 136.5 mg. The reported comparison is a mean difference of -29.9 mg, with bupivacaine minus placebo as the direction of comparison. The subtraction describes the contrast between the group means; it does not adjust for other characteristics.

What does the mean difference describe?

A mean difference expresses how far apart the two group averages are on the original outcome scale. Its sign depends on the order of subtraction. With bupivacaine minus placebo, a negative value indicates a lower observed mean in the bupivacaine group. The difference refers to group averages, not the experience of every participant. Individual outcomes can vary around each group mean, as the standard deviations indicate.

In general, a standard deviation describes the spread of individual observations around a group mean. It is not the same as a standard error, which describes uncertainty in an estimated quantity such as a mean. The registry record supplies group standard deviations, but it does not report individual-level data, distributions, or an analysis that adjusts for other variables. The means and standard deviations alone cannot describe all features of the outcome distribution.

How should the confidence interval be read?

The 95% confidence interval for the primary mean difference runs from -82.39 mg to 22.59 mg. In general, a confidence interval gives a range of values reasonably compatible with the data and the method used to calculate it. It reflects uncertainty in the estimated contrast; it is not a guarantee that the true difference lies inside the particular interval. Because this interval crosses zero, the summaries do not rule out a zero difference. The range also includes values in both directions, so the estimate does not determine the direction of the underlying difference with precision.

The confidence interval and p-value are related ways of conveying uncertainty, but they are not interchangeable descriptions. The unadjusted p-value for this comparison is 0.264. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it is not a measure of the clinical importance of an effect. The registry record does not report a formal sponsor analysis or its testing assumptions for the primary outcome; this p-value belongs to the unadjusted recalculation from the posted summaries.

Why does variation matter?

When individual values vary widely, a group mean can be estimated less precisely unless the study has enough information to offset that variation. In general, greater variability makes it harder to distinguish a group contrast from sampling variation. The standard deviations for the primary outcome are large relative to the reported means, and the confidence interval is broad. These features help explain why the point estimate alone is not a complete account of the evidence. No inference about the shape of the outcome distribution should be made from the means and standard deviations alone.

Over-dispersion is a general concern when observed variation is greater than a statistical model expects. In that situation, a model that understates variability may produce overly narrow uncertainty intervals or overly optimistic tests. The registry record does not describe a model for the primary outcome, report a dispersion assessment, or provide information that establishes whether over-dispersion occurred. It would therefore be inappropriate to claim that a particular model was used or that a dispersion adjustment was needed.

What is and is not reported about the analysis?

The registry record reports no formal primary or secondary analyses. The comparisons discussed are unadjusted recalculations from posted group summaries. The record does not report whether the trial used an intention-to-treat, per-protocol, or other analysis population; how participants were handled if they did not receive the planned infusion; how missing data were treated; or whether an adjusted model was planned. These are distinct analysis choices, and the outcome summaries do not resolve them.

In general, an adjusted analysis can account for prespecified covariates or design features, while an unadjusted comparison uses the groups’ outcome summaries without such adjustment. Neither description by itself determines which approach is more appropriate; that depends on the trial design and analysis plan. Here, the registry record does not report enough detail to characterize any sponsor-selected model or to compare it with the recalculated contrast. The discrepancy flag is false, so there is no posted inconsistency that would require a different reported comparison to take precedence.

The same caution applies to secondary outcomes. Their unadjusted comparisons are useful as descriptive summaries, but testing several outcomes can increase the chance that at least one apparently unusual result arises by chance. In general, multiplicity procedures account for a family of tests or otherwise frame confirmatory claims. The registry record does not report whether any multiplicity strategy was prespecified or used. That absence limits how strongly individual secondary p-values can be interpreted.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of -29.9 mg, with a 95% confidence interval from -82.39 mg to 22.59 mg. This interval is wide enough to include zero and values on either side of it. It therefore indicates uncertainty not only about the size of the mean difference but also about its direction. The confidence interval is more informative about that uncertainty than the point estimate alone.

In general, a confidence interval describes the range of estimates compatible with the data under the calculation’s assumptions. It does not mean there is a 95% probability that the particular true difference lies within this one interval. The interval’s width reflects sampling uncertainty and the variability and amount of outcome information available. The registry record does not report a formal sponsor analysis or additional model-based precision estimates for this endpoint.

The posted outcome summaries include 44 participants in the bupivacaine group and 46 in the placebo group, alongside standard deviations of 117.2 mg and 136.5 mg. The observed variation and the available outcome counts are relevant context for the uncertainty, but the registry record does not explain why these counts differ from overall enrollment or identify any missing-data process. No conclusion about why the interval has its particular width can be assigned to an unreported cause.

Precision is not the same as importance. A narrow interval can estimate a small difference precisely, while a broad interval can leave substantial uncertainty about a potentially meaningful range of differences. The posted primary interval leaves that uncertainty unresolved. It should not be read as proof of equivalence or as proof that a particular benefit or harm exists.

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 for this continuous outcome are expressed as participants per arm, not as total events. The illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to 100%, 75%, and 50% of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a planning scenario designed to have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and model assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not guarantees about the result of a future study. For the primary outcome, the illustration lists 286 participants per arm for 80% power and 382 participants per arm for 90% power when planning for 100% of the observed effect. Planning for 75% of the observed effect gives 507 participants per arm for 80% power and 679 participants per arm for 90% power. Planning for 50% gives 1,141 participants per arm for 80% power and 1,527 participants per arm for 90% power.

The curve represents the general relationship between the target effect and the required planning sample size under these assumptions: smaller effects require more participants to detect than larger effects. These calculations are planning illustrations based on the observed effect, not observed power. The trial’s own design assumptions are not reported, so the illustration should not be treated as a reconstruction of the study’s original sample-size calculation.

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 = -29.900; pooled standard deviation σ = 127.435.
2. n = 2 × (1.96 + 0.842)² × 127.435² / -29.900² = 285.1, rounded up to 286 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 <- -29.9                      # observed difference in means
sigma <- 127.435026671348                     # 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(2601027)
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 = 286 (80% power), 382 (90% power)
 75% of observed effect: n per arm = 507 (80% power), 679 (90% power)
 50% of observed effect: n per arm = 1,141 (80% power), 1,527 (90% power)
power.t.test: 286.1 
Simulated power at n = 286 per arm: 0.800 (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. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a multiplicity strategy, or a hierarchy of confirmatory and exploratory outcomes. It lists several secondary outcomes in addition to the primary OME endpoint, and the posted results include unadjusted comparisons for several of them. Without a reported plan, it is not possible to determine whether the tests were treated as a family, whether any adjustment was used, or how the study intended to interpret secondary findings.

In general, multiplicity arises when several hypotheses or outcomes are tested. Each test has uncertainty, and the chance of at least one apparently unusual result can increase across a collection of tests. A multiplicity procedure can control that risk under a defined testing strategy; alternatively, results may be explicitly interpreted as exploratory. Neither approach can be attributed to this trial from the registry record. The unadjusted anti-emetic p-value should therefore be interpreted with that limitation in mind, rather than as conclusive evidence on its own.

The registry record also does not report the primary analysis population, the treatment of missing outcome data, or participant flow for the posted endpoint. It gives outcome group sizes of 44 and 46, but does not explain their relationship to enrollment of 120. It does not state whether all randomized participants were analyzed in their assigned groups, whether any exclusions occurred, or whether missing measurements were imputed or otherwise handled. These details matter because analysis populations and missing-data methods can affect both estimates and uncertainty.

The absence of these details does not demonstrate that a particular method was or was not used. It means the registry record does not allow readers to assess those choices. No assumption should be made about interim analyses, stopping rules, covariate adjustment, or a prespecified approach to missingness; those details are not reported in the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for 64 participants at risk in the bupivacaine group and 56 at risk in the placebo group. It reports zero serious adverse events in each group and zero deaths in each group. These counts describe the safety reporting groups in the registry record; they are not the same denominators as the primary outcome summaries.

For other, non-serious adverse events, the registry reports 21 affected participants among 64 at risk in the bupivacaine group and 27 among 56 at risk in the placebo group. These are participant counts, not event rates calculated. The registry record does not provide serious adverse event terms, and it does not explain why the adverse-event denominators differ from the primary outcome denominators.

Zero reported serious events should be read as a description of the entries in this record, not as evidence that serious events are impossible or that a safety difference has been ruled out. The registry record does not report an analysis comparing adverse-event groups, confidence intervals for these counts, or further detail about ascertainment. The counts alone do not establish a causal safety conclusion.

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

The primary result describes a lower observed mean OME in the bupivacaine group than in the placebo group during the first 48 hours after surgery. The estimated unadjusted mean difference is -29.9 mg, with a 95% confidence interval from -82.39 mg to 22.59 mg and an unadjusted p-value of 0.264. The interval includes zero and spans differences in both directions. The posted summaries therefore leave uncertainty about the size and direction of the underlying group difference.

This result does not prove that the groups are equivalent, and it does not prove that one group has lower OME use in the broader population. A nonzero point estimate is not enough to establish a dependable difference, while an interval that includes zero does not establish that any possible difference is absent. The statistical summary is best understood as an estimate with appreciable uncertainty.

The trial’s design was randomized, double-blind, and parallel-group, which describes important features of how the comparison was organized. Those labels do not supply missing information about participant flow, adherence, outcome completeness, analysis populations, or the exact statistical plan. The registry record does not report those details, so the posted comparison cannot be interpreted as an adjusted or otherwise prespecified analysis.

The secondary summaries offer context but do not settle the primary question. In particular, the unadjusted anti-emetic comparison is one result among multiple listed outcomes, and the registry record does not report a multiplicity strategy. The numeric results for time to first bowel movement and quality of life measurement are not reported in the registry record. Those gaps limit broad conclusions about recovery outcomes.

Finally, the results apply to the outcomes and groups described in this registry record. They do not establish effects for different populations, procedures, infusion regimens, or follow-up periods. The statistics describe the posted data and their uncertainty; they are not medical advice and do not determine an individual treatment decision.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated difference should be read together with its uncertainty. The primary point estimate is negative, but the confidence interval includes zero and extends into positive values. Looking only at the direction or size of the estimate would omit important information about how precisely the comparison is known. The interval makes clear that the posted summaries do not resolve the direction of the underlying difference.

It also shows the distinction between a trial’s overall enrollment and the number of participants included in a particular outcome summary. Enrollment is listed as 120, while the primary outcome summaries include 44 and 46 participants in the two groups. The registry record does not explain this difference. Recognizing the distinction helps prevent readers from assuming that every enrolled participant contributed to every posted endpoint.

The trial is statistically informative beyond its primary estimate because the registry also lists distinct secondary outcomes and safety counts. Those results need to be interpreted according to their own measures and uncertainty, while accounting for the absence of a reported multiplicity strategy and analysis plan. An unadjusted secondary p-value can attract attention, but it does not automatically have the same evidential role as a prespecified primary analysis.

Finally, planning calculations based on an observed effect are not evidence about the study’s achieved power or original design rationale. They illustrate how assumptions about a target effect and desired power relate to participant requirements. Keeping those planning concepts separate from the observed trial result is essential when using registry summaries to assess precision.

18. Limitations

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

Several trial-specific limitations follow from what the registry record does not report. Although the study is marked randomized and double-blind, the record does not give details of sequence generation, allocation concealment, masking implementation, or participant flow. It reports enrollment of 120 but gives primary outcome counts of 44 and 46, without explaining the difference or describing exclusions and missing observations. This leaves uncertainty about which participants contributed to the endpoint summaries.

The primary outcome is reported as a group mean and standard deviation, with an unadjusted recalculated comparison. No formal sponsor analysis, adjusted model, analysis population, or missing-data method is reported in the registry record. The interval is broad and includes zero. These features limit the precision and interpretability of the primary estimate; they do not identify why the uncertainty is present.

The outcome itself combines narcotic use through conversion to OME, but the registry does not report further detail about the conversion procedure, handling of individual medication records, or whether the observed distribution was assessed. It also does not report the trial’s original sample-size justification or assumptions. The planning illustration based on the observed effect should not be mistaken for those original design decisions.

For secondary outcomes, the registry record does not report a multiplicity strategy, and numeric findings are not reported for time to first bowel movement or quality of life measurement. The adverse-event denominators differ from the primary outcome denominators, with no explanation in the record. These gaps limit how completely the results can be assessed across efficacy and safety outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Transversus Abdominis Plane Block in Microsurgical Breast Recon w/Abdominal Free Flap in Breast CA — NCT02601027.
• Registry record last updated 2021-09-23; status last verified 2021-08.
• Results first posted 2021-09-23.
• 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.

22. Record Summary

The registry record describes NCT02601027 as a completed, randomized, double-blind, parallel-group Phase III study sponsored by Stanford University. It lists enrollment of 120 and a study start of 2015-11, with primary completion on 2019-09-07. Patients undergoing abdominal free flap-based breast reconstruction were assigned to a 0.125% bupivacaine infusion or a saline placebo infusion through a TAP catheter.

The primary outcome was OME use during the first 48 hours after surgery. Posted means were 139.3 mg for bupivacaine and 169.2 mg for placebo; the unadjusted recalculated mean difference was -29.9 mg, with a 95% confidence interval from -82.39 mg to 22.59 mg and p = 0.264. The interval includes zero, leaving uncertainty about the direction and size of the difference.

The record does not report formal analyses, the original sample-size justification, multiplicity handling, analysis populations, or missing-data methods. Secondary findings and safety counts should be interpreted with those limitations in mind.