Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors (NCT02351700), a randomized phase 4 study. The primary outcome is Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour).

2. Clinical Question

This is a comparison of assigned analgesia regimens, not a comparison of ibuprofen alone with no pain treatment: both groups were assigned acetaminophen, and the control group could receive rescue narcotics. The registry labels the trial randomized and double-blind, with parallel groups. Its brief summary describes 100 treated subjects and planned groups of 50, while the primary outcome results list 28 and 34 participants in the two arms. The reason for that difference is not reported in the registry record.

3. Trial Design

The registry identifies this as a randomized, double-blind, parallel-group, Phase 4 intervention trial. It is marked completed. The listed start date is 2015-02-01 and the primary completion date is 2016-03-01. The sponsor is St. Joseph's Hospital and Medical Center, Phoenix. The study concerns pain management after trans-sphenoidal surgery for pituitary tumors.

The active regimen used intravenous ibuprofen, identified as Caldolor, with scheduled oral acetaminophen. The comparator used intravenous placebo with the same scheduled acetaminophen. Both regimens were intended to continue during the hospital stay or for 48 hours, whichever came first. The record also mentions rescue treatment for breakthrough pain. The full rescue protocol is not reported in the registry record. Although the trial is described as double-blind, details about who was masked and how masking was maintained are not reported in the registry record.

The registry's brief summary describes 100 treated subjects, with 50 assigned to each group. However, the posted primary outcome results report 28 participants in the opioid-sparing group and 34 in the standard treatment group. These figures describe different parts of the record; the reason for the discrepancy is not reported in the registry record. The recorded enrollment is 62. The record does not explain the relation between the enrollment figure, the brief summary's treatment target, and the outcome counts.

The primary outcome was mean pain score over 48 hours. The registry describes pain measurement every 4 hours and a 0-10 scale. It also lists seven outcome measures and two posted secondary outcomes, while the analysis count is zero and no reported analyses are listed for the secondary outcomes. The original statistical analysis plan, the trial's own sample-size assumptions, and the handling of repeated measurements are not reported in the registry record.

4. Participant Flow and Accounting

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

Before assignment: Randomized 1:1 ratio with blinded treatment assignment. Used a computer-generated list from random.org.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants enrolled with the intent to treat.

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: Patients age \>18 years and \<80 years undergoing endonasal transsphenoidal surgery for pituitary adenoma.

6. Primary Endpoint

The registry lists the primary outcome as Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour), measured over mean pain score over 48 hours.

The primary endpoint is mean pain score over 48 hours, measured on a 0-10 Visual Analog Scale. The registry describes pain ratings every 4 hours. The scale runs from 0, no pain, to 10, worst possible pain; higher scores represent worse pain. The endpoint is a continuous measure, and the registry reports a mean and standard deviation for each group.

A mean gives a summary of the recorded pain scores across the measurement period. Comparing group means therefore addresses the average reported pain under the two assigned regimens, rather than the experience at one isolated time point. It does not show how scores changed over time, whether some participants had very different experiences from others, or how many participants crossed any particular pain threshold. Those details are not reported in the registry record.

Repeated pain ratings can provide information across the postoperative period, but measurements from the same participant are related rather than independent observations. A statistical analysis of the repeated measurements would need to account for that relationship if it used the individual ratings directly. The registry reports a mean pain score over 48 hours but does not report how the repeated ratings were combined, how missing ratings were handled, or whether the analysis used the repeated observations or a participant-level summary.

The endpoint is relevant to the stated comparison because pain is the intended outcome of the analgesia regimens. It is nevertheless a summary: the mean does not convey the full distribution of scores, the timing of pain, or the use of rescue medication. The registry does not report a threshold for a clinically important difference, so the size of a mean difference cannot be classified against such a threshold from this record alone.

7. Results Posted in the Registry

• Opioid-sparing Group: mean 1.70 versus 2.80 on control; difference -1.10 (95% CI -2.40 to 0.20), standardized effect d = -0.41; z-test p = 0.096.

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.

Breakthrough Narcotic Requirement

• 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:
  • Opioid-sparing Group: mean 26.30 versus 62.50 on control; difference -36.20 (95% CI -60.14 to -12.26), standardized effect d = -0.71; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Opioid-sparing Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover breakthrough narcotic requirement and other adverse events. The posted breakthrough narcotic summary points in the same broad direction as the primary mean pain estimate: the opioid-sparing group has a lower reported mean. This correspondence can make the findings appear coherent across different measures, but the outcomes are not interchangeable. Pain scores reflect reported pain, whereas narcotic requirement reflects rescue medication use and can also depend on clinical decisions and the rescue-treatment protocol.

The adverse-event summaries do not show a single uniform pattern across the two groups: serious events are recorded in the standard treatment group, while other adverse events are recorded in the opioid-sparing group. These small counts are descriptive and do not establish comparative safety. The registry's serious-event terms include epistaxis, but the record does not provide enough context to infer a causal relationship or to compare the groups reliably on that term.

The secondary findings relate to the primary result as additional, distinct outcomes rather than confirmation of the primary endpoint. The registry lists two posted secondary outcomes but reports no analyses for them. The posted summary-based narcotic comparison has an unadjusted result, and no adjustment for multiple outcomes is reported. When several outcomes are examined, chance alone can produce apparently notable findings; without a prespecified hierarchy or multiplicity approach, isolated unadjusted results carry less weight than a clearly specified primary analysis.

These outcomes can help describe the overall pattern, but they do not resolve the uncertainty in the primary pain comparison. Nor can their results establish that differences are clinically important. Definitions, analysis plans, missing-data handling, and full event-level details are not reported in the registry record. The secondary outcomes should therefore be interpreted as exploratory descriptions of the posted record rather than as independent definitive evidence.

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

• Breakthrough Narcotic Requirement
• Other Adverse Events

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, so the registry reports a mean pain score and standard deviation for each treatment group. A mean describes the central level of observed scores, while a standard deviation describes how dispersed participant scores are around that mean. The opioid-sparing group mean was 1.7 with a standard deviation of 2.2; the standard treatment group mean was 2.8 with a standard deviation of 3.0. Averages are useful for comparing groups, but they do not show the full distribution or whether participants had similar experiences.

What does the mean difference represent?

The posted comparison is expressed as the opioid-sparing group mean minus the standard treatment group mean. The estimated difference is -1.1. A negative value means the first group's mean was lower on the stated pain scale. Since higher scores represent worse pain, the estimate points toward lower average pain in the opioid-sparing group. The sign gives the direction of the contrast; it does not by itself establish whether the difference is reliable or important.

How should the confidence interval be read?

A confidence interval describes uncertainty around an estimate under the statistical method used. It gives a range of values reasonably compatible with the observed data and method; it is not a guarantee that the true effect lies within the particular interval. For the primary comparison, the posted interval crosses zero. Zero represents no difference between the group means, so the interval includes both no difference and values on either side. This indicates that the estimate is not precise enough to distinguish clearly between those possibilities. The registry does not report the method used to construct this interval.

What does the p-value say?

The unadjusted p-value is 0.096. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of an effect. The registry does not report a threshold for interpreting this p-value or a multiplicity plan. It should therefore be read alongside the estimated difference, interval, analysis details, and the fact that other outcomes were recorded.

Why does variation matter?

Standard deviations of 2.2 and 3.0 show that pain scores varied among participants in both groups. When individual observations are spread out, a mean difference can be estimated less precisely unless the data contain sufficient information. The standard deviation is not the uncertainty interval for the mean difference: it describes variation among scores, whereas the confidence interval describes uncertainty about the group contrast. The registry does not report the underlying score distributions, so skewness, clustering at particular scale values, or unusual observations cannot be assessed from the means and standard deviations alone.

What is special about repeated pain ratings?

The registry says pain was measured every 4 hours over 48 hours and reports a mean over that period. Ratings from one participant are likely to be related because they come from the same person over time. In general, analyses of repeated measurements need to account for within-person dependence if they use each time point as an observation. Treating related ratings as independent can understate uncertainty. The registry does not report whether the endpoint was formed by averaging participant-level ratings, whether all time points were included, or what statistical model was used.

Other potentially relevant analysis choices are not reported in the registry record. These include how missing ratings were treated, whether any adjustment variables were used, how participants were handled if they did not follow the assigned regimen, and whether the comparison was performed according to randomized assignment. The primary population is described as all participants enrolled with intent to treat, but the record does not provide further detail about implementation of that approach. The registry lists no reported analyses and gives no sponsor analysis for the posted primary comparison.

What does the effect-size estimate add?

The posted standardized effect estimate is -0.412. A standardized effect expresses the group difference relative to a measure of variability, allowing results measured on different scales to be compared in principle. It does not translate directly into a clinically meaningful change, and its interpretation depends on the population and variability. It should not replace the scale-specific mean difference, whose units are points on the 0-10 pain scale.

These methods describe how to interpret summaries, not a reconstruction of the trial's unreported statistical plan. The posted mean difference, interval, and p-value are based on the summaries recorded for the comparison. The record does not establish whether they reproduce the trial investigators' prespecified analysis.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -1.1 points on the 0-10 pain scale. Its confidence interval extends from -2.396 to an upper endpoint of 0.197. Because zero falls within the interval, the data are compatible with no difference in group means as well as with a difference in either direction. The interval is relatively broad in relation to the point estimate, so the estimated direction is more certain than the exact size of any difference is not: the size remains imprecise.

Confidence intervals are useful because they place the point estimate in context. The point estimate alone might suggest lower mean pain in the opioid-sparing group, but the interval shows that uncertainty includes a small value on the other side of zero as well as more negative values. This should not be read as proof of equivalence or as proof that there is no difference. Equivalence requires a prespecified margin and an appropriate design and analysis; such a margin is not reported in the registry record.

The group standard deviations, 2.2 and 3.0, also indicate variation in pain scores. They are not confidence limits and do not directly tell the reader how precise the difference is. The interval for the comparison is the more direct summary of uncertainty in the group contrast. The registry does not report a clinically important threshold for the scale, so the interval cannot be judged against a recorded threshold for meaningful change.

Interpretation is further limited by unreported analysis details: the method for combining repeated ratings, treatment of missing measurements, and any adjustment strategy are not stated. The reported outcome counts are also not reconciled with the brief summary's planned treatment counts. These gaps make it difficult to assess how much the posted interval reflects the planned analysis or the full randomized population.

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 report of the trial's original design calculations. They give participants per arm for 80% power and participants per arm for 90% power; they are not total sample sizes. The registry's planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. These calculations use the observed effect and do not describe the trial's own design assumptions, which are not reported in the registry record.

For each assumed effect size, the 80% power column gives the planning count per arm for a design with an 80% chance of detecting an effect of that size under the stated assumptions, if the assumed effect and model were correct. The 90% power column uses a higher target chance of detection and therefore requires more participants per arm in the listed scenarios. These are prospective design quantities, not measures of what the completed trial achieved.

The rows consider planning for 100%, 75%, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so more participants are needed to reach the same target power under otherwise unchanged assumptions. The figures do not show that the trial had the stated power, and they are not observed power. They are illustrations whose validity depends on assumptions that may not hold in a future study, including the assumed effect size and equal allocation.

The posted outcome counts differ from the brief summary's planned treatment counts, and the record does not explain the difference. The sample-size illustrations should therefore be read as planning scenarios based on the posted observed comparison, not as an account of recruitment targets, enrollment decisions, or the adequacy of the completed trial's size.

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 = -1.100; pooled standard deviation σ = 2.670.
2. n = 2 × (1.96 + 0.842)² × 2.670² / -1.100² = 92.5, rounded up to 93 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 <- -1.1                      # observed difference in means
sigma <- 2.66983145535444                     # 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(2351700)
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 = 93 (80% power), 124 (90% power)
 75% of observed effect: n per arm = 165 (80% power), 221 (90% power)
 50% of observed effect: n per arm = 370 (80% power), 496 (90% power)
power.t.test: 93.4 
Simulated power at n = 93 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. Multiplicity, Missing Data and Analysis Populations

The registry reports a primary pain outcome and lists secondary outcomes, including breakthrough narcotic requirement and other adverse events. It does not report how many hypotheses were tested in the investigators' analysis, whether secondary outcomes were prespecified in a hierarchy, or whether a multiplicity adjustment was used. Without that information, an unadjusted p-value for a secondary outcome does not account for the possibility that several outcomes were examined. In general, testing multiple outcomes increases the chance that at least one result appears unusual by chance. This is why secondary results without a stated multiplicity plan deserve more caution than a single prespecified primary comparison.

The registry's analysis count is zero, and no reported analyses are listed for the secondary outcomes. The record does not state whether this means analyses were not conducted, were not submitted, or were recorded elsewhere. It also does not report a full statistical analysis plan, interim analyses, or stopping rules. These elements should not be inferred from the randomized, double-blind design.

Missing-data handling is also not reported. The primary population is described as all participants enrolled with the intent to treat, but the record does not state how missing pain scores, withdrawals, protocol deviations, or incomplete follow-up were addressed. An intent-to-treat description does not by itself establish how missing outcomes were handled or whether every randomized participant contributed to the reported summary.

The primary results list 28 participants in the opioid-sparing group and 34 in the standard treatment group. The registry's enrollment is 62, while the brief summary describes 100 treated subjects and planned groups of 50. The reason for this difference is not reported in the registry record. The record also does not clarify whether the reported outcome counts represent all randomized participants, participants with available endpoint data, or another analysis set.

These omissions affect interpretation, not just reporting completeness. Without a stated analysis plan, missing-data approach, and reconciliation of the participant counts, readers cannot fully evaluate the analysis population, the risk of selective reporting, or whether the posted estimates follow the planned methods.

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 serious adverse event terms

Most frequent non-serious adverse event terms

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

The serious adverse event summaries list 28 participants at risk in the opioid-sparing group, with 0 serious adverse events, and 34 at risk in the standard treatment group, with 2 serious adverse events. Deaths are recorded as 0 in both groups. The record lists 2 other adverse events in the opioid-sparing group and 0 in the standard treatment group, with the corresponding at-risk counts of 28 and 34.

These are small descriptive counts. They do not establish that either regimen caused or prevented an event, and they do not provide a precise comparison of safety. The registry lists epistaxis at 5.9% among the serious adverse event terms; it does not report group attribution for that term in the posted serious-event summary. The record does not provide event narratives, timing, severity criteria, or details of relatedness assessment.

The at-risk counts are the denominators recorded for these summaries. They should be read with the group event counts rather than treated as proof that all participants had the same duration of observation or complete safety follow-up. Additional safety follow-up and event definitions are not reported in the registry record.

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

The primary result is an estimated difference in average pain scores over 48 hours, not a direct measure of every participant's experience. The opioid-sparing group's mean score was lower than the standard treatment group's mean, and the estimated difference was -1.1 points on the stated scale. The confidence interval crosses zero, so the posted data do not establish a clear difference in average pain. The result should be described with both its direction and its uncertainty.

The comparison concerns two treatment packages. Both included scheduled acetaminophen; the opioid-sparing regimen included intravenous ibuprofen, while the standard group received intravenous placebo and could receive rescue narcotics. The findings cannot isolate the effect of any one component, and the registry does not provide enough detail about the rescue-treatment protocol to assess how rescue use shaped pain scores.

A result that is not statistically clear is not evidence that the regimens are equivalent. Equivalence or non-inferiority requires a suitable design, a prespecified margin, and an analysis capable of addressing that question. Such a margin and analysis are not reported in the registry record. Conversely, the direction of a point estimate does not establish a meaningful or reliable advantage. The record does not report a threshold for a clinically important difference in pain scores.

The secondary outcome summaries provide additional context but do not settle the primary uncertainty. They involve different measures, and the registry does not report a multiplicity plan or completed analyses for those outcomes. The adverse event counts are also too limited and incompletely described to support broad comparative safety conclusions from the record alone.

Interpretation is constrained by unreported details about missing measurements, the repeated-rating analysis, adherence, and the analysis population. The brief summary's planned treatment counts also differ from the primary outcome counts, without an explanation in the registry record. The data therefore describe the posted estimates for this trial but do not, by themselves, establish a general result for other settings or patient populations.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate, an uncertainty interval, and the study record's design details must be considered together. The primary estimate has a clear direction, but its confidence interval includes zero. Reporting only the group means could overstate certainty; reporting the estimate with its interval makes the remaining uncertainty visible.

The endpoint also raises a common issue in clinical research: repeated ratings from the same participant are correlated. A 48-hour summary can be useful, but its interpretation depends on how repeated pain ratings were reduced or modeled. Because that analysis method is not reported, readers cannot assess whether the statistical treatment of the time series matched the data structure.

The record gives a practical example of the distinction between a primary endpoint and secondary outcomes. A secondary result may appear more statistically compelling, yet it is not automatically confirmatory, especially when multiplicity procedures and prespecified analysis priorities are not reported. The outcome family and the analysis plan matter when interpreting p-values.

It also highlights the importance of reconciling participant counts across registry fields. The enrollment, brief summary, and outcome counts do not tell the same story about treatment numbers, and the explanation is not recorded. Clear accounting of randomized participants, treated participants, and outcome availability is necessary for evaluating the analysis population and the reach of the results.

Finally, the sample-size illustrations distinguish planning calculations from the trial's own design rationale. They show how assumed effect size and target power influence a future planning scenario; they cannot establish whether the completed study was adequately sized or what power it achieved. The original design assumptions are not reported in the registry record.

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 affect how the posted results can be interpreted. The primary outcome is described as pain measured every 4 hours and summarized over 48 hours, but the registry does not state how these repeated ratings were combined or analyzed. It also does not report whether all planned measurements were available or how missing ratings were handled. This prevents assessment of the analysis model and the completeness of the endpoint.

Participant counts are not reconciled across the record. Enrollment is listed as 62, the brief summary describes 100 treated subjects and planned groups of 50, and the primary results list 28 and 34 participants. The reason for the differences is not reported in the registry record. Without a participant flow or analysis-population explanation, it is difficult to determine who contributed to the reported outcome summaries.

The record does not provide the original sample-size justification, statistical analysis plan, multiplicity approach, or details of any interim analysis. It also does not report adherence, protocol deviations, or how the double-blind procedures were implemented. These omissions limit evaluation of whether the reported comparisons match prespecified methods.

The primary comparison is based on group means and standard deviations, without posted score distributions or a clinically important difference threshold. The confidence interval crosses zero, and the record does not provide additional analysis that resolves this uncertainty. The secondary outcomes are listed without reported analyses, and the safety summaries provide only limited event counts and descriptions. No causal interpretation of individual adverse events can be made from those summaries.

These limitations arise from what the registry record reports; they do not establish that the study team did not conduct further analyses or collect additional information. Such details are simply not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors — NCT02351700.
• Registry record last updated 2021-10-21; status last verified 2019-11.
• Results first posted 2021-10-21.
• 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 describes a completed, randomized, double-blind, parallel-group, Phase 4 trial of analgesia after trans-sphenoidal surgery for pituitary tumors. It compares an opioid-sparing regimen using intravenous ibuprofen and scheduled acetaminophen with standard treatment using intravenous placebo and scheduled acetaminophen. The primary outcome is mean pain score over 48 hours on a 0-10 scale.

The posted primary means are 1.7 and 2.8, with an estimated mean difference of -1.1. The confidence interval crosses zero, and the unadjusted p-value is 0.096. The record also lists breakthrough narcotic requirement and adverse events. The reason for differing participant counts across registry summaries is not reported in the registry record.