Analgetic and Anxiolytic Effect of Preoperative Pregabalin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analgetic and Anxiolytic Effect of Preoperative Pregabalin (NCT00353704), a randomized phase 4 study. The primary outcome is Mean VAS Pain (Visual Analogue Scale)at Rest (0-100 mm).

2. Clinical Question

The central comparison is between participants allocated to pregabalin and those allocated to placebo. The primary endpoint is a continuous pain score, with larger values indicating worse pain. The registry record reports arm means and standard deviations, along with an unadjusted mean difference and confidence interval. Those data describe the observed group results and the precision of the estimated difference; they do not by themselves establish how outcomes would generalize to other surgical settings or populations.

The intervention was tested as premedication, rather than as a treatment initiated after pain was measured. The registry description also names morphine as an intervention, and cumulative morphine consumption is posted as a secondary outcome at 240 minutes. The record does not post an anxiety outcome measure. It therefore does not permit an assessment of the anxiety question stated in the study purpose.

3. Trial Design

The registry describes a completed phase 4, randomized, quadruple-masked, parallel-group study sponsored by Asker & Baerum Hospital. The recorded conditions are intervertebral disk displacement and disk prolapse. Enrollment is listed as 50. The registry dates the study start to 2005-11 and primary completion to 2009-05.

Participants were assigned to pregabalin or placebo. The pregabalin arm received 150 mg orally about one hour before surgery; the placebo arm received one oral saccharose capsule at about the same time. The record identifies morphine among the interventions, and cumulative opioid consumption is also posted as a secondary outcome. The meaning of each masking role, the allocation procedure, and the specific implementation of randomization are not reported in the registry record.

For the primary outcome, the registry reports data for 22 participants in the pregabalin arm and 24 in the placebo arm. These outcome-specific counts are not the same as the enrollment figure, and the reasons for the difference are not reported in the registry record. The record does not state whether every randomized participant was included in the outcome analysis or how missing outcome values were handled.

The primary endpoint was mean VAS pain at rest 120 minutes after surgery. A secondary outcome was cumulative morphine consumption at 240 minutes. Although the study purpose mentions anxiety before anaesthesia, an anxiety result is not posted. The registry record does not report the trial's original sample-size justification, planned analysis population, or a detailed statistical analysis plan. It lists no reported analyses.

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.

Overall Study

Reasons for not completing this period:

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 Mean VAS Pain (Visual Analogue Scale)at Rest (0-100 mm), measured over 120 minutes after surgery.

The primary endpoint is mean pain intensity at rest 120 minutes after surgery, measured with a visual analogue scale from 0 to 100 mm. A score of 0 represents no pain and 100 represents maximal pain; higher values indicate a worse outcome. The registry reports the endpoint in scale units and summarizes it as a mean with standard deviation in each arm.

A continuous pain scale preserves more gradation than a simple yes-or-no outcome. Comparing group means gives a concise description of the average scores in the two randomized arms. The mean difference expresses the contrast in the original scale units, so its direction and size can be read against the 0–100 mm scale. It does not describe every participant's experience: individuals can have scores above or below their group's mean, and the standard deviation describes spread within each arm.

Pain at rest at a fixed postoperative time is a specific snapshot. It should not be read as a measure of pain at all times, pain during movement, longer-term recovery, or anxiety. The registry records morphine consumption separately as a secondary measure at 240 minutes, which reflects a different aspect of postoperative care. The time points and outcomes therefore answer related but distinct questions.

For the primary endpoint, the posted mean is 11.7 in the pregabalin arm and 22.5 in the placebo arm. The posted mean difference is -10.8 scale units, with a 95% confidence interval from -17.82 to -3.78. A negative difference reflects a lower observed mean in the pregabalin arm under the comparison's stated direction.

7. Results Posted in the Registry

• Pregabalin: mean 11.70 versus 22.50 on control; difference -10.80 (95% CI -17.82 to -3.78), standardized effect d = -0.87; z-test p = 0.003.

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.

Morphine (Opioid) Consumption Cumulated

• 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:
  • Pregabalin: mean 7.30 versus 16.00 on control; difference -8.70 (95% CI -14.60 to -2.80), standardized effect d = -0.83; z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Pregabalin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary endpoint is cumulative morphine consumption at 240 minutes. Its group contrast follows the same direction as the primary pain-at-rest result: the reported mean is lower in the pregabalin arm than in the placebo arm. This directional consistency may be relevant when considering whether the outcomes tell a coherent descriptive story, but the measures are not interchangeable. Pain intensity is a reported experience at a specified time, while cumulative opioid consumption is medication use over a specified period.

The two endpoints also have different timeframes and units. The secondary result is an outcome in milligrams at 240 minutes, whereas the primary result is a VAS score at 120 minutes. A consistent direction does not show that one outcome caused the other, nor does it show that both outcomes capture the same underlying effect. The posted results support describing their observed directions, not attributing a mechanism.

The secondary comparison is unadjusted. The registry record does not report a multiplicity strategy, so the result should carry less evidential weight than a prespecified primary comparison when judging the overall findings. When several outcomes are examined, the chance of seeing at least one apparently notable result can increase; general statistical practice may address that issue through a prespecified testing hierarchy or adjustment, but whether either was used is not reported in the registry record.

The record lists no reported analyses and does not post an anxiety result, although anxiety is mentioned in the study purpose. It is therefore not possible to assess how the secondary endpoint fitted into a broader analysis plan or how many additional outcomes or comparisons were considered. The secondary pattern is best treated as supporting descriptive information, rather than independent confirmation that resolves uncertainty in the primary comparison.

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

• Morphine (Opioid) Consumption Cumulated

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numeric score on a visual analogue scale. For a continuous measure, an arm mean summarizes the central value of the observed scores, while a standard deviation describes their spread around that mean. The primary arm means are 11.7 with a standard deviation of 9.6 for pregabalin and 22.5 with a standard deviation of 14.4 for placebo. A mean is useful for a concise comparison, but it does not show the full distribution or identify how many participants had any particular score.

What does the mean difference represent?

The mean difference is the pregabalin group mean minus the placebo group mean, according to the comparison direction used in the posted results. The primary estimate is -10.8 scale units. A negative value indicates that the observed mean was lower in the pregabalin arm. Because the endpoint is scored so that higher values represent worse pain, the direction indicates a lower average score in that arm. The estimate is expressed in the endpoint's own units rather than as a standardized quantity.

The arm-level standard deviations and the difference answer different questions. The mean difference describes the contrast between group averages; each standard deviation describes variability among participants within one arm. Neither is a description of every individual's response. The posted mean difference and interval are based on the group summaries, and the registry record does not give a fuller account of the analysis model, covariates, or any adjustments.

How should the confidence interval be read?

A confidence interval conveys uncertainty in an estimated contrast. In general statistical terms, an interval is calculated by a procedure that, under its assumptions, would cover the underlying parameter at its stated rate over repeated applications. It is not a guarantee that the particular interval contains the true value, and it is not an interval containing a stated proportion of individual outcomes. The primary 95% confidence interval runs from -17.82 to -3.78 scale units. Its endpoints are both below zero, which is compatible with a lower mean score in the pregabalin arm under the stated comparison direction.

The interval also communicates precision: a narrower interval represents less uncertainty about the contrast than a wider interval, all else equal. Precision depends on factors such as the amount of information and the variability in the observed data. The arm counts are 22 and 24, and the standard deviations are 9.6 and 14.4. The registry does not report a detailed account of how the confidence interval was constructed, so the exact analysis assumptions cannot be assessed from the record.

What does the unadjusted p-value say?

The primary unadjusted p-value is 0.003. In general, a p-value measures how incompatible the observed data, or more extreme data, are with a specified null model, when that model and the test assumptions are used. It is not the probability that the null hypothesis is true, nor the probability that the result occurred by chance. The registry does not report a full statistical analysis plan or identify a multiplicity adjustment. The p-value therefore describes the posted unadjusted comparison, not an analysis accounting for every outcome or test that may have been considered.

The comparison is labeled as a mean difference, but detailed methods for the original sponsor analysis are not reported in the registry record. The listed analysis count is zero. The comparison statistics can be read as unadjusted estimates accompanying the posted summary results; the record does not give the testing procedure, model diagnostics, or a description of any covariate adjustment. No assumptions beyond those explicitly posted should be inferred.

Why can variability matter?

General statistical explanation: when individual outcomes vary substantially within groups, the group means may be less precisely estimated for a given amount of information. A standard deviation helps describe that variability. If continuous outcomes have a distribution with more variability than a chosen model expects, a model that does not account for that over-dispersion can understate uncertainty. The registry does not report an over-dispersion assessment, a distributional diagnostic, or a method specifically addressing it. This is a general consideration, not a claim that over-dispersion occurred in this trial.

The VAS scale is bounded from 0 to 100 mm. A mean and standard deviation are familiar summaries for a continuous endpoint, but the registry record does not provide individual scores or distribution plots. It is therefore not possible from the record to assess the shape of the score distribution, the presence of floor or ceiling patterns, or how closely a normal approximation describes these data.

What is the role of randomization and masking?

Random allocation is intended, in general, to make groups comparable at the start of a trial on average, including with respect to factors that are not measured. Masking is intended to reduce the influence of knowledge about assigned treatment on care, outcome assessment, or reporting. The registry labels this study randomized and quadruple-masked. It does not explain who was masked, how assignment was generated or concealed, or whether masking was maintained. Those details are not reported in the registry record and cannot be inferred from the labels alone.

Randomization does not remove uncertainty in a small trial, prevent missing outcomes, or guarantee that all analyses preserve the benefits of assignment. The registry does not report an analysis population or the handling of participants with unavailable outcomes. The primary comparison should therefore be understood as the contrast among the posted arm summaries, with the extent to which those summaries include all randomized participants not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -10.8 scale units, and its 95% confidence interval extends from -17.82 to -3.78. The interval gives a range of plausible values for the group contrast under the calculation's assumptions. Its placement entirely below zero is consistent with a lower observed mean VAS score in the pregabalin arm. The estimate is not a guarantee of an effect of exactly -10.8 in a broader population; the interval expresses uncertainty around the estimate.

The interval's width matters alongside its direction. It shows that the data are compatible with a range of negative mean differences, rather than pinpointing one exact value. The group means and standard deviations offer context for the estimate, but they do not replace the interval: variability among participants and uncertainty in the group contrast are related but distinct concepts. Individual scores may vary beyond the interval because the interval concerns the mean difference, not individual outcomes.

The unadjusted p-value for the primary comparison is 0.003. It is one summary of compatibility with a null model and should be read together with the effect estimate and interval. The registry does not report an adjustment for multiple testing, and it does not provide enough detail to evaluate all assumptions underlying the interval or test. Thus, the posted precision is conditional on the analysis used and the available outcome data.

For the secondary morphine outcome, the posted mean difference is -8.7 mg, with a 95% confidence interval from -14.6 to -2.799 and an unadjusted p-value of 0.004. This estimate also has uncertainty and should be interpreted as a separate outcome comparison. The registry's lack of a reported multiplicity plan and analysis details limits how strongly either interval or p-value can be treated as confirmatory evidence across outcomes.

The primary outcome counts are 22 and 24. The registry record does not explain why these counts differ from the enrollment figure of 50, whether any endpoint data were missing, or whether the interval accounts for all randomized participants. That information would be relevant to assessing precision and potential bias. The posted confidence intervals describe statistical uncertainty under the analysis, not uncertainty introduced by unreported missingness or design details.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total participants. The calculation uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects set at 100%, 75%, and 50% of the observed effect. For each assumed effect, the 80% power column gives the participants per arm indicated by that planning calculation for an 80% chance of rejecting the null model if the assumed effect and calculation assumptions hold. The 90% power column gives the corresponding per-arm count for a 90% chance.

The primary-endpoint planning illustration gives 21 participants per arm for 80% power and 28 for 90% when planning for 100% of the observed effect. For 75% of the observed effect, it gives 37 per arm for 80% power and 49 for 90%. For 50% of the observed effect, it gives 83 per arm for 80% power and 110 for 90%. The secondary-endpoint illustration uses its own observed effect and gives different planning counts.

Smaller effects are harder to distinguish from random variation, so the calculation calls for more participants per arm when the assumed effect is reduced. Increasing the target power also calls for more participants per arm. These figures are planning illustrations based on the observed effect, not a report of the trial's original design assumptions. The original sample-size justification is not reported in the registry record. This is not observed power.

13. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = -10.800; pooled standard deviation σ = 12.344.
2. n = 2 × (1.96 + 0.842)² × 12.344² / -10.800² = 20.5, rounded up to 21 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 <- -10.8                      # observed difference in means
sigma <- 12.3441557758391                     # 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(353704)
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 = 21 (80% power), 28 (90% power)
 75% of observed effect: n per arm = 37 (80% power), 49 (90% power)
 50% of observed effect: n per arm = 83 (80% power), 110 (90% power)
power.t.test: 21.5 
Simulated power at n = 21 per arm: 0.795 (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 how multiplicity was handled. The primary pain endpoint and the secondary morphine-consumption endpoint are both posted, and anxiety is named in the study purpose without a posted anxiety result. When researchers test more than one outcome or comparison, unadjusted p-values do not account for the possibility that one result may appear notable because multiple tests were performed. An analysis plan can specify which endpoint is primary, how secondary outcomes are interpreted, and whether adjustments or a testing sequence are used. Those details are not reported in the registry record.

The primary comparison has an unadjusted p-value of 0.003, and the secondary comparison has an unadjusted p-value of 0.004. Those values should not be interpreted as multiplicity-adjusted evidence. The record does not establish whether additional endpoints, time points, or analyses were planned or conducted. It lists zero reported analyses, so the full set of analyses underlying the posted results cannot be evaluated from the record.

Missing-data handling is also not reported in the registry record. Enrollment is 50, whereas the primary outcome data are reported for 22 participants in the pregabalin arm and 24 in the placebo arm. The record does not explain the difference, state whether outcome data were unavailable, or indicate how any missing values were handled. It does not say whether participants were analyzed according to their randomized assignment or under another analysis population.

These omissions matter because excluding participants or handling missing values differently can alter group summaries and uncertainty. General statistical methods for missing data rely on assumptions about why observations are missing; those assumptions cannot be evaluated without information about the missingness and analysis approach. No particular missing-data mechanism or method can be inferred.

The registry identifies randomization and quadruple masking but does not report the allocation procedure, masking roles, protocol deviations, or analysis population. It also does not report an interim-analysis plan. These omissions do not establish that a problem occurred; they mean that the corresponding safeguards and decisions cannot be assessed from the registry record.

15. Safety Results

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

Other (non-serious) adverse events

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

The registry lists zero serious adverse events affecting participants in the pregabalin group, among 22 at risk, and zero in the placebo group, among 24 at risk. It also lists zero other adverse events affecting participants in both groups, with the same group counts at risk. No serious adverse-event terms are listed. Death counts are not reported in the registry record.

These are event counts as recorded, not a complete narrative of safety monitoring. A zero count means no events of the listed type are recorded as affecting participants in those groups in this entry; it does not establish that no event occurred outside the registry's reporting definitions or observation period. The registry record does not provide a detailed list of event definitions, collection procedures, or follow-up duration for safety outcomes.

The trial's enrollment and group sizes are limited, and a study of this size may provide little information about uncommon events. This is a general statistical consideration, not a claim that uncommon events occurred. The listed figures should not be used to infer that there is no risk, or to compare safety beyond what these recorded counts describe.

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

The results describe average outcomes for the participants whose data are posted. For the primary pain-at-rest endpoint, the observed mean was lower in the pregabalin group than in the placebo group at 120 minutes after surgery. The unadjusted mean difference and confidence interval convey the direction, scale, and statistical uncertainty of that comparison. The secondary morphine-consumption result has the same observed direction, at its own time point and in its own units.

These are trial results, not a guarantee about any individual's outcome. Group averages do not establish that every participant experienced a lower score or used less morphine. Nor do these measurements answer questions about other kinds of pain, later recovery, anxiety, or outcomes not reported. The study purpose mentions anxiety before anaesthesia, but an anxiety outcome is not posted in the registry record.

The registry describes randomization and masking, but it does not give enough detail to assess their implementation. It also does not report the original sample-size justification, the analysis population, missing-data handling, or a detailed multiplicity plan. Outcome-specific counts do not match the enrollment figure, and the reason is not reported in the registry record. These gaps restrict the assessment of how complete and robust the posted comparisons are.

The unadjusted p-values and confidence intervals should be read as statistical summaries conditional on the analyses and data represented in the record. They do not establish causation by themselves, and they do not remove uncertainty about selection, missing outcomes, or the range of analyses considered. The secondary result is informative as a descriptive pattern but carries less weight in the absence of a reported multiplicity strategy.

In general, applying a trial result beyond its enrolled participants requires considering how closely other populations, procedures, and care settings resemble the trial context. The record identifies vertebral-column surgery and conditions related to disk displacement or prolapse, but it does not provide a detailed description of participants or surgical procedures. The findings should therefore be understood within the reported study context rather than assumed to apply uniformly elsewhere.

17. Why This Trial Matters Statistically

This trial illustrates the distinction between a point estimate and its uncertainty. The primary mean difference communicates the direction and size of the observed contrast on the VAS scale, while its confidence interval shows that the estimate is not exact. Reading both together is more informative than relying on a p-value alone.

It also demonstrates why endpoint definitions and timing matter. Pain at rest was measured 120 minutes after surgery, whereas cumulative morphine consumption was recorded at 240 minutes. These are related postoperative measures, but they capture different outcomes over different time frames. Their same-direction pattern is descriptively coherent, yet does not make them interchangeable or establish a causal pathway between them.

The record provides a practical setting for considering multiplicity and reporting completeness. There is a posted primary result and a secondary result, while anxiety is named in the study purpose but has no posted result. Without a reported analysis plan, it is not possible to determine how outcomes were prioritized or whether statistical testing was adjusted. This limits the strength of conclusions drawn from unadjusted secondary evidence.

Finally, the enrollment figure and endpoint-specific counts raise questions that cannot be resolved from the registry record. The reasons for the differing counts, missing-data procedures, and analysis population are not reported. Statistical interpretation depends not only on calculating estimates, but also on knowing which participants contributed and how outcomes were handled. The record shows why transparent reporting of those details is important for evaluating precision and potential bias.

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.

The primary outcome data are posted for 22 participants in the pregabalin group and 24 in the placebo group, while total enrollment is listed as 50. The registry record does not explain this difference or state whether all randomized participants contributed to the endpoint summaries. It also does not report reasons for missing or excluded outcomes, if any. This leaves the completeness of the endpoint data uncertain.

The study purpose includes anxiety before anaesthesia, but no anxiety outcome is posted. The record therefore does not permit statistical assessment of that stated question. The listed secondary endpoint is cumulative morphine consumption at 240 minutes; the registry does not post other secondary results or analyses.

Further details that would help assess the estimates are not reported in the registry record: the original sample-size justification, a full statistical analysis plan, the analysis population, the exact method used for the comparisons, handling of missing values, and any multiplicity strategy. The record also does not describe the randomization procedure, allocation concealment, masking roles, or protocol deviations. Their absence from the record should not be taken as evidence that a particular procedure was or was not used.

The posted group summaries do not show individual scores or outcome distributions. Consequently, the distributional shape, possible floor or ceiling patterns, and the influence of unusually high or low observations cannot be assessed. The fixed primary measurement time gives a specific postoperative snapshot, not a summary of pain over a longer period. These limitations are specific to what the registry reports and do not establish that the trial's underlying conduct was deficient.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Analgetic and Anxiolytic Effect of Preoperative Pregabalin — NCT00353704.
• Registry record last updated 2011-07-20; status last verified 2011-07.
• Results first posted 2011-07-20.
• 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

NCT00353704 is a completed phase 4 randomized, quadruple-masked, parallel-group study sponsored by Asker & Baerum Hospital. The registry lists enrollment of 50 and describes oral pregabalin 150 mg about one hour before surgery compared with an oral saccharose placebo.

The primary outcome is mean VAS pain at rest 120 minutes after surgery. The posted mean difference is -10.8 scale units, with a 95% confidence interval from -17.82 to -3.78 and an unadjusted p-value of 0.003. The secondary outcome is cumulative morphine consumption at 240 minutes; its unadjusted comparison is in the same direction.

The registry record does not report an anxiety result, the original sample-size justification, detailed analysis methods, multiplicity handling, or missing-data procedures. Primary endpoint group counts are 22 and 24, and the reason they differ from the enrollment figure is not reported in the registry record.