Evaluation of the Efficacy and Safety of HTX-011 for Postoperative Analgesia Following Abdominoplasty Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Efficacy and Safety of HTX-011 for Postoperative Analgesia Following Abdominoplasty Surgery (NCT02689258), a randomized phase 2 study. The primary outcome is Summed Pain Intensity Scores Collected Over 24 Hours.

2. Clinical Question

3. Trial Design

NCT02689258 is a completed Phase 2 randomized, double-masked, parallel-group study of postoperative analgesia following abdominoplasty surgery. The official title describes an evaluation of HTX-011 or HTX-002. The registry lists enrollment of 277 and a start date of 2016-02-23, with primary completion recorded as 2017-03. The sponsor is Heron Therapeutics.

The overall record includes several parts and cohorts, with HTX-011A, HTX-011B, HTX-002, bupivacaine HCl, and saline placebo represented among the interventions. Dose, formulation, and route vary across the listed cohorts. For example, the posted primary comparison is specifically Part A, Cohort A: HTX-011A, against the saline-placebo group identified as Parts A and B, Cohort B. It should not be treated as a comparison of every active group against placebo.

The primary result uses 20 participants in the HTX-011A arm and 63 in the saline-placebo arm. These are the group sizes for this endpoint comparison, not a restatement of overall enrollment. The registry names the analysis population as mITT, but the definition of that population and the handling of exclusions are not reported in the registry record.

Randomized, double-masked, and parallel describe the broad design, but the registry record does not report details such as the randomization sequence, allocation concealment, masking procedures, or the planned statistical analysis. The trial is marked completed. The posted results include the primary continuous outcome and safety counts, while secondary outcome results 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: 1 Subject underwent complete abdominoplasty and was unintentionally randomized to receive HTX-002 (intended for mini-abdominoplasty procedure only). This subject is included in the Safety, ITT, and mITT Populations.

Only the first 6 of 12 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: mITT Population.

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.

Population: Study HTX-011-203 included multiple study parts, various study drugs, formulations, and administration techniques. It was pre-specified in the SAP to pool different doses of the same study drug within study parts for Participant Flow, Baseline Characteristics, and AEs. We pooled different doses of the same study drug within study parts for Participant Flow, Baseline Characteristics, and AEs. However for Outcome Measures, different doses of study drugs were presented separately.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Summed Pain Intensity Scores Collected Over 24 Hours, measured over 24 hours.

The primary endpoint is the summed pain intensity score collected over 24 hours, reported as a mean in units on a scale. The registry describes SPI0-24 as a weighted sum of pain-intensity scores at scheduled assessment times. Each score contributes according to the scheduled duration since the prior assessment, so the measure incorporates both the recorded intensity and the time represented by that assessment.

The stated scale ranges from 0 to 240: 0 corresponds to a pain-intensity score of 0 at every assessment, and 240 corresponds to a score of 10 at every assessment. As a general interpretation, a larger summed score represents more accumulated pain intensity over the measurement period. A weighted summary can be useful when a research question concerns pain experience across a period rather than a single assessment. That is a general description of the measure, not evidence that this endpoint captures every aspect of pain or recovery.

The registry lists the primary outcome timeframe as 24 hours and identifies the mITT Population. The posted group summaries are means with standard deviations. The outcome’s detailed assessment schedule is described in the registry, but the registry record does not report how missing assessments were handled or whether any imputation was used.

7. Results Posted in the Registry

• Part A, Cohort A: HTX-011A: mean 92.60 versus 96.16 on control; difference -3.56 (95% CI -27.03 to 19.91), standardized effect d = -0.08; z-test p = 0.766.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a group mean describe?

The endpoint is continuous, and the registry reports a mean for each group. A mean summarizes the average score among the participants included in that group’s analysis. It condenses the observed scores into one value, but it does not show the full distribution or imply that every participant had a score near the mean.

The registry also reports a standard deviation for each group. In general, a standard deviation describes how dispersed participant measurements are around the group mean. It is different from the standard error, which describes uncertainty in an estimated mean. The reported standard deviations are 47.53 for HTX-011A and 43.77 for saline placebo. These are measures of participant-level variation, not confidence limits for the mean.

How should the mean difference be read?

The posted mean difference is -3.56 units, using the HTX-011A mean relative to the saline-placebo mean. A difference of zero would mean equal group means for this endpoint. A negative estimate means the HTX-011A mean was lower in the posted data; the sign alone does not show whether the difference is important to patients or attributable to treatment.

In general, a comparison of means estimates a group-level contrast. It does not say that each individual in one group had a better or worse outcome than each individual in the other group. The reported estimate concerns the endpoint and analysis population specified in the registry, rather than every outcome or every cohort in the trial.

What does the confidence interval add?

A confidence interval expresses uncertainty around an estimate under the statistical procedure used. The posted 95% interval is -27.03 to 19.91 units. In general, a confidence interval is not a guarantee that the true value lies inside the particular interval, nor is it a range containing 95% of participant scores. It is a way to communicate how compatible the data are with different values of the underlying contrast under the model and assumptions used.

Because this interval includes zero and extends into both negative and positive values, it does not isolate a single direction of difference. Its interpretation also depends on the analysis being appropriate for the data and on the assumptions used to calculate it. The registry record does not describe those calculation details.

What does the p-value mean?

The unadjusted p-value is 0.766. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions were true. It is not the probability that the null hypothesis is true, the probability that the result occurred by chance, or a measure of clinical importance. A relatively large p-value does not establish equality between groups.

The registry identifies the value as unadjusted. The exact statistical test, sidedness, model details, and any prespecified testing sequence are not reported in the registry record. The p-value should therefore be read alongside the estimate and confidence interval, rather than as a stand-alone verdict.

Why can variation matter?

In general, greater variation among participant measurements can make a mean difference harder to estimate precisely, especially when group sizes are limited. The observed standard deviations describe variation in this endpoint. The confidence interval conveys uncertainty about the contrast itself; it is not interchangeable with either group’s standard deviation. Differences in group size also affect the precision of a comparison, but the registry record does not report a rationale for the group allocation in this comparison.

Over-dispersion is a general statistical concern when observed variability exceeds what a model assumes. If a model understates variability, its uncertainty estimates can be too narrow. Whether over-dispersion was assessed or relevant to the analysis in this trial is not reported in the registry record, and no such issue should be inferred from the summary values alone.

What does the mITT label tell the reader?

The primary outcome is associated with the mITT Population. This tells the reader the registry’s name for the population used in the result, but the record does not define which randomized participants were included, how post-randomization events were handled, or whether the analysis followed assigned groups. Those details cannot be inferred from the label alone.

In general, analysis-population definitions can affect which observations contribute to an estimate and how the result relates to the randomized comparison. Missing outcome data can also affect means and uncertainty, depending on their amount, reasons, and handling. The registry record does not report the missing-data method or the completeness of primary endpoint measurements.

What is not specified about the analysis?

The record reports the group summaries, mean difference, confidence interval, and unadjusted p-value, but it does not report the full statistical analysis plan. Details such as model specification, covariate adjustment, assumptions checks, missing-data procedures, and any planned sensitivity analyses are not reported in the registry record. These are not interchangeable with the calculations that can be made from posted summary statistics.

The registry contains several treatment cohorts and identifies three outcome measures. In general, testing multiple outcomes or comparisons can raise multiplicity concerns because repeated testing can increase the chance of a nominally unusual result. The reported p-value is unadjusted, and the trial’s own multiplicity strategy is not reported in the registry record. No adjustment should be assumed either way.

10. Confidence Intervals and Precision

The key precision measure for the primary contrast is the 95% confidence interval, from -27.03 to 19.91 units around the reported mean difference of -3.56. It spans zero, so the estimate does not pin down whether the underlying group-mean contrast is negative or positive. The interval also communicates that the data allow a range of magnitudes, not just values close to the point estimate.

In general, a confidence interval is a statistical uncertainty summary for an estimated quantity. It is not an interval for individual participant scores, and it does not mean that the probability of the true value being inside this particular interval is 95%. Its practical interpretation depends on the analysis method and assumptions. The registry record does not describe the precise method used to produce the interval.

The group means were 92.6 for HTX-011A and 96.16 for saline placebo. Their standard deviations, 47.53 and 43.77 respectively, describe spread in participant scores, whereas the interval around the mean difference describes uncertainty in the comparison. These quantities answer different questions and should not be substituted for one another.

The reported interval does not establish equivalence or rule out a meaningful difference. The registry record does not report a threshold for clinical importance, a prespecified equivalence margin, or an analysis designed to test equivalence. Precision is therefore best described in terms of the breadth and direction-spanning nature of the interval, without assigning clinical meaning that the record does not supply.

11. 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 participants per arm for 80% power and participants per arm for 90% power. They are illustrations based on the observed effect in the posted comparison, not the original trial’s sample-size calculation. The 80% column describes a planning scenario with an 80% chance of detecting the specified effect under the stated assumptions if that effect is the true one; the 90% column uses a higher target chance of detection. Neither column describes the power achieved by the completed trial.

The planning 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 as the stated fraction of the observed effect. For planning at 100% of the observed effect, the figures are 2,474 participants per arm for 80% power and 3,311 participants per arm for 90% power. Planning at 75% of the observed effect gives 4,397 participants per arm for 80% power and 5,886 participants per arm for 90% power. At 50% of the observed effect, the figures are 9,893 participants per arm for 80% power and 13,244 participants per arm for 90% power.

Smaller effects require more participants to detect under otherwise fixed assumptions, which is why the planning figures increase as the target fraction decreases. These values are not a recommendation for a future study and do not account for assumptions beyond those stated. The trial’s own original design assumptions and sample-size justification are not reported in the registry record. These are planning illustrations, not observed power.

12. 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 = -3.560; pooled standard deviation σ = 44.684.
2. n = 2 × (1.96 + 0.842)² × 44.684² / -3.560² = 2,473.1, rounded up to 2,474 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 <- -3.56                      # observed difference in means
sigma <- 44.6843886911716                     # 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(2689258)
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 = 2,474 (80% power), 3,311 (90% power)
 75% of observed effect: n per arm = 4,397 (80% power), 5,886 (90% power)
 50% of observed effect: n per arm = 9,893 (80% power), 13,244 (90% power)
power.t.test: 2474.1 
Simulated power at n = 2,474 per arm: 0.803 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a multi-part study with several treatment groups and cohorts, and it lists three outcome measures. The posted primary result is the HTX-011A versus saline-placebo comparison for summed pain intensity over 24 hours. The record does not post secondary outcome results. The unadjusted p-value for the primary comparison is 0.766.

When several hypotheses are tested, multiplicity can make a nominal p-value less informative unless the testing strategy is planned and interpreted appropriately. This is a general statistical issue. Whether the trial’s own analysis controlled family-wise error, used a hierarchy, selected a primary comparison in advance, or applied another strategy is not reported in the registry record. The presence of multiple cohorts alone does not reveal which comparisons were prespecified or how they were handled.

The primary analysis population is labeled mITT. The registry record does not report the operational definition of that population, the number of participants with evaluable endpoint data, or the reasons for any exclusions. It also does not report the amount or pattern of missing endpoint data, the method used to handle missing observations, or sensitivity analyses for missingness. These omissions limit assessment of how robust the posted result is to analysis-population choices and incomplete measurements.

The statistical model and test details are not reported in the registry record. That includes whether covariates were used, whether assumptions were checked, and whether an adjusted estimate was also produced. The trial’s protocol-level statistical plan, interim analyses, and sample-size justification are not reported in the registry record. None should be inferred from the registry’s designation of the study as randomized, double-masked, or Phase 2.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: wound dehiscence (5.9%).

The registry reports serious adverse events for the listed safety groups. The counts were zero among 20 participants in Part A, Cohort A: HTX-011A; zero among 63 in the saline-placebo group identified as Parts A and B, Cohort B; zero among 48 in Part A, Cohorts C Through F: HTX-011B; zero among 17 in Part B, Cohort A: HTX-002; one among 77 in Part C, Cohort A Through C: HTX-011B; one among 17 in Part C, Cohort D: Bupivacaine HCI; and zero among 32 in Part C, Cohort E: Saline Placebo. Deaths were reported as zero for each listed group.

The registry lists wound dehiscence at 5.9% among the leading serious adverse-event terms, but does not identify a group for that term in the posted summary. The term should not be assigned to a particular treatment arm based on the information in the record.

These are descriptive counts across groups with differing treatments and cohort definitions. They are not, by themselves, a controlled estimate of comparative safety. The registry also reports other adverse events, but the summaries do not provide enough detail to judge event type, timing, severity, or causal attribution. Absence of a reported serious event in a group does not establish absence of risk.

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

The posted primary result is a comparison of average 24-hour summed pain intensity scores for HTX-011A and saline placebo in the registry’s mITT Population. The HTX-011A mean was 92.6 and the placebo mean was 96.16. The estimated mean difference was -3.56 units, and its 95% confidence interval ranged from -27.03 to 19.91. The unadjusted p-value was 0.766. Together, these statistics describe a point estimate that is slightly negative and an interval that leaves substantial uncertainty about the direction and size of the group-mean contrast.

The result does not establish that the groups are the same. It also does not establish a clinically important difference, because the registry record does not report a threshold for clinical importance. A non-significant p-value is not proof of no effect, and the interval should not be treated as evidence of equivalence. Those conclusions would require different criteria or analyses not reported in the record.

The posted comparison concerns one dose and route in one cohort against a specified saline-placebo group. Other parts of the study included HTX-011B, HTX-002, and bupivacaine HCl in different cohorts. The result therefore cannot be generalized automatically to every listed intervention, dose, route, or cohort. Nor does a 24-hour pain endpoint answer every question about postoperative recovery or longer-term outcomes.

The registry’s safety summaries provide descriptive serious-event and death counts for several groups, but they do not establish comparative safety. Differences in cohort membership and treatment mean those counts should not be interpreted as a single head-to-head safety analysis. The record does not report detailed statistical comparisons of adverse events.

Overall, the record supports a precise description of the posted means and their uncertainty, but leaves important analysis details unspecified. Interpretation should remain confined to this registry comparison and should not be turned into medical advice or a claim that a treatment works or does not work.

16. Why This Trial Matters Statistically

This trial is statistically interesting because its record includes a direct continuous-outcome comparison, but places that result within a broader study containing several parts, cohorts, and interventions. That structure makes it important to distinguish the specific HTX-011A versus saline-placebo estimate from the trial’s other treatment groups. A result from one cohort is not an overall estimate for all formulations or doses.

The endpoint is a time-weighted summary of pain-intensity measurements over 24 hours. Such a measure gives a single group-level score for a defined postoperative period, while retaining the contribution of scheduled intervals. Its interpretation nevertheless depends on the assessment schedule and the way incomplete measurements were handled; missing-data details are not reported in the registry record.

The difference estimate and interval also illustrate why point estimates should not be read alone. The estimated contrast is -3.56 units, but its 95% confidence interval extends from -27.03 to 19.91. The reported p-value is 0.766 and is unadjusted. The combination points to uncertainty, not a definitive conclusion of equality or a quantified clinical benefit. This distinction is central to sound interpretation of clinical trial summaries.

Finally, the registry supports some descriptive reporting while leaving other questions open. It identifies the mITT Population and posts group means, standard deviations, an interval, and safety counts. It does not report the detailed analysis-population definition, missing-data methods, multiplicity strategy, or full statistical plan. Recognizing that boundary is part of interpreting registry results responsibly.

17. 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 primary comparison has unequal group sizes: 20 participants in the HTX-011A arm and 63 in the saline-placebo arm. The registry record does not explain the allocation across these comparison groups or report a justification for the numbers included in the endpoint analysis. Overall enrollment is 277, but that figure should not be confused with the group sizes used for this posted comparison.

The record labels the population mITT without defining it. It does not report how many participants had a measured primary outcome, whether all randomized participants contributed, or what happened to missing assessments. Without these details, readers cannot assess the potential impact of exclusions or missing data on the estimated group means.

Only the primary comparison is accompanied by a posted estimate in the results used for this analysis; secondary outcome results are not reported in the registry record. The record lists other arms and cohorts, but does not provide their primary-comparison estimates. The multiple cohorts, formulations, doses, and routes limit any attempt to generalize the HTX-011A result across the entire study.

The mean difference is reported with an unadjusted p-value, while the exact test, model, analysis assumptions, multiplicity plan, and prespecified clinical-importance threshold are not reported in the registry record. The 95% confidence interval is broad and spans values on both sides of zero. These limitations do not invalidate the posted result, but they constrain how strongly it can be interpreted.

The trial concerns postoperative analgesia following abdominoplasty surgery and reports the primary endpoint over 24 hours. The registry record does not establish whether the findings apply to other surgical settings, other time periods, or outcomes beyond the recorded measures. Safety summaries are descriptive and do not provide a detailed adjusted comparison across groups.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluation of the Efficacy and Safety of HTX-011 for Postoperative Analgesia Following Abdominoplasty Surgery — NCT02689258.
• Registry record last updated 2026-03-02; status last verified 2026-02.
• Results first posted 2023-10-04.
• 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.

21. Record Summary

NCT02689258 is a completed Phase 2 randomized, double-masked, parallel-group trial sponsored by Heron Therapeutics. It evaluated HTX-011 or HTX-002 for postoperative analgesia following abdominoplasty surgery and records enrollment of 277 participants.

The posted primary outcome is the mean summed pain intensity score over 24 hours in the mITT Population. For HTX-011A versus saline placebo, the means were 92.6 and 96.16, respectively, with a mean difference of -3.56, a 95% confidence interval from -27.03 to 19.91, and an unadjusted p-value of 0.766.

The registry lists several additional treatment cohorts and provides descriptive safety counts. It does not report secondary outcome results, the detailed mITT definition, missing-data methods, or the trial’s multiplicity strategy. The primary estimate is therefore best read as a specific comparison with uncertainty, rather than as an overall conclusion about all treatments in the study.