Anesthesia and Postoperative Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anesthesia and Postoperative Pain (NCT00232817), a randomized phase 4 study. The primary outcome is Score on a Pain Rating Scale (Numerical Analog Score).

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 4 randomized, parallel-group trial with triple masking. The brief summary describes the study as prospective and double-blinded. These are the descriptions recorded in the registry; further detail about who was masked and how masking was maintained is not reported in the registry record.

The study concerns two anesthetic contexts, isoflurane and propofol, and an additional randomization to intranasal nicotine or placebo. The arm descriptions refer to propofol anesthesia with and without nicotine and isoflurane anesthesia with and without nicotine. However, the posted outcome groups are named only “Nicotine” and “Placebo.” Their reported primary comparison therefore summarizes those two groups without displaying separate estimates for each anesthetic context.

The registry records enrollment of 23. Its brief summary states that 80 adult women undergoing uterine surgery would be recruited, while the enrollment field reports 23. The posted primary and secondary outcome groups each list 10 participants per group. Participant flow, reasons for the difference between the planned recruitment described in the summary and the enrollment recorded, and the number included in each analysis are not reported in the registry record.

The study status is completed. The record gives a start of 2003-07 and primary completion of 2005-07. The sponsor is Columbia University. Beyond the broad study description, detailed allocation procedures, eligibility criteria, treatment administration details, and the original analysis plan 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.

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 Score on a Pain Rating Scale (Numerical Analog Score), measured over Up to 24 hours.

The primary outcome is the mean score on a Numerical Rating Scale for pain, reported in scores on a scale. The scale runs from 0, meaning no pain, to 10, meaning worst pain. Pain was assessed at 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 120, and 1440 minutes after surgery, and the average across all listed time points is reported. The stated timeframe is up to 24 hours.

An average across repeated assessments gives a single summary of pain ratings over the measurement period. In general, this can make a complex series of observations easier to compare between groups, while also obscuring when differences occurred or whether they varied over time. The registry reports the average outcome rather than the individual time-point results, so the posted summary does not describe the trajectory of pain ratings across those assessments.

The study’s broader question concerns pain in the context of two anesthetics and the potential pronociceptive action of isoflurane. The posted primary outcome is compared by nicotine versus placebo, without separate reported results for each anesthetic context. Consequently, the reported average-score contrast alone does not show whether the nicotine-placebo pattern differs between the isoflurane and propofol groups.

7. Results Posted in the Registry

• Nicotine: mean 1.50 versus 4.90 on control; difference -3.40 (95% CI -4.32 to -2.48), standardized effect d = -3.23; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Cumulative Morphine Usage

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Nicotine: mean 35.30 versus 51.60 on control; difference -16.30 (95% CI -38.38 to 5.78), standardized effect d = -0.65; z-test p = 0.148.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nicotine and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary endpoint: cumulative morphine usage up to 24 hours. Its group comparison points in the same general direction as the primary outcome contrast, but the estimate is less precise and the interval includes zero. The secondary finding therefore does not provide a clear, independent confirmation of the primary pattern.

The two outcomes describe related but distinct aspects of the postoperative period. The primary measure is an average of reported pain ratings across the listed assessment times; the secondary measure is cumulative morphine usage. Agreement between outcomes can sometimes strengthen a coherent interpretation, while differences can reflect that outcomes measure different constructs, have different variability, or are analyzed with different precision. The registry does not provide further analyses that explain the relationship between these measures.

The secondary comparison is unadjusted. In general, when multiple outcomes or contrasts are tested, the chance of obtaining at least one apparently unusual result can increase. Whether and how to adjust depends on the prespecified testing strategy and the scientific question. The registry record does not report a multiplicity plan or adjusted secondary results, so the secondary result should be treated as exploratory evidence rather than as a definitive test independent of the primary outcome.

No additional secondary outcomes are posted in the record, and no reported secondary analyses are listed. That limits the assessment to the single recorded secondary endpoint and does not establish that no other analyses were conducted. The registry does not report whether the secondary outcome was designated as confirmatory, how it was prioritized, or whether its analysis was prespecified.

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

• Cumulative Morphine Usage

9. Statistical Interpretation

10. Statistical Methods Explained

Continuous outcomes are described using a mean and a standard deviation. The mean is the arithmetic average of the measured values. The standard deviation describes how dispersed individual observations are around that average; it is not the uncertainty of the mean itself. For the primary pain outcome, the reported mean and standard deviation are 1.5 and 0.5 for nicotine, and 4.9 and 1.4 for placebo. The group sizes are 10 in each group.

What does the mean difference represent?

The reported mean difference compares the nicotine group with the placebo group. For the primary outcome, the estimate is -3.4. A negative value indicates that the reported mean is lower for nicotine than for placebo, using the comparison’s stated ordering. The estimate describes the average contrast between these posted groups. It is not a statement about every participant, and it does not show how an individual’s pain score changed over time.

In general, a difference in means is a direct summary for a continuous outcome measured on the same scale in both groups. Its interpretation depends on the scale and on what the groups represent. Here the outcome is an average pain score on a scale with endpoints described as 0 for no pain and 10 for worst pain. Because the registry posts a single comparison by nicotine and placebo, rather than separate contrasts within each anesthetic group, the estimate should not be read as an anesthetic-specific treatment effect.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the observed data and the statistical procedure used, under its assumptions. It communicates uncertainty around an estimated contrast. The primary 95% confidence interval runs from -4.321 to -2.479. Since the entire interval is below zero, the values in that interval all indicate a lower average score for nicotine than placebo under the comparison’s ordering. The interval does not account for every possible source of uncertainty, such as unreported missingness, analysis choices, or limitations in the trial design.

In general, a narrower interval indicates greater precision for the particular estimate, while a wider interval indicates less precision. Interval width is affected by the amount of information in the data and the variability of the outcome. The group sizes are small, so the displayed confidence interval should be understood as uncertainty around this comparison, not as a guarantee that the same range applies in other settings or groups.

How should the p-value be read?

The primary unadjusted p-value is <0.001. In general, a p-value measures how unusual results at least as inconsistent with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not a measure of the size or importance of an effect, and it is not the chance that the findings are due to chance. The term “unadjusted” means the reported p-value is not stated to account for the testing of multiple outcomes or contrasts. The registry record does not report a multiplicity procedure.

A p-value should be read alongside the estimate and confidence interval. The estimate gives the direction and magnitude of the observed group contrast; the interval describes its precision; the p-value summarizes compatibility with a null model. None of these quantities by itself establishes the validity of the study’s assumptions or resolves the question of whether the reported comparison answers the full anesthesia-specific research question.

Why do dispersion and outcome timing matter?

For a continuous outcome, variability within each group affects how precisely a difference in group means can be estimated. The posted standard deviations show that individual pain scores vary around each group mean. The primary outcome averages ratings across multiple postoperative times. That summary can be useful for comparing overall reported pain during the period, but it removes information about whether an observed group contrast was larger at some times and smaller at others. The registry lists assessment times but does not post time-specific estimates.

In general, over-dispersion matters most directly in count or rate models, where the observed variability exceeds what a basic model expects; it can lead to underestimated uncertainty if ignored. The posted primary outcome is continuous and analyzed as a mean, so over-dispersion is not the central issue described by this summary. The registry does not report the detailed statistical model or diagnostics, so further assumptions about the analysis cannot be evaluated from the record.

The reported comparisons are unadjusted group summaries. The registry does not report covariate-adjusted estimates, an intention-to-treat definition, a per-protocol analysis, or the handling of missing outcome measurements. Those omissions matter because they leave unclear exactly which participants and observations contributed to the estimates and whether any prespecified adjustment was used.

11. Confidence Intervals and Precision

The primary mean difference is -3.4, with a 95% confidence interval from -4.321 to -2.479. The interval is entirely below zero, indicating that the reported range of values is consistent with a lower average pain score in the nicotine group than in the placebo group, according to the comparison’s ordering. The interval also shows that the estimate is not a single exact value: the data and analysis are compatible with a range of contrasts.

In general, a confidence interval describes uncertainty from sampling under the assumptions of the statistical method. It does not include every kind of uncertainty. For example, it does not by itself resolve potential effects of missing observations, choices made during analysis, measurement limitations, or whether the posted groups fully represent the intended anesthesia-specific comparisons. The registry record does not report enough detail to assess those issues.

The primary comparison contains 10 participants in each group. The relatively small group counts are important context when considering how stable the estimate may be. The confidence interval reflects the reported comparison and its statistical method, but the registry does not provide individual participant data or additional estimates that would show how much the result depends on particular observations.

The secondary outcome has a mean difference of -16.3 mg, with a 95% confidence interval from -38.38 to 5.781. This interval includes zero, so the posted estimate is compatible with values on either side of no difference. The registry also reports an unadjusted p-value of 0.148. Compared with the primary result, the secondary outcome does not show the same degree of precision around a direction of difference. The distinction is about the evidence and uncertainty in these posted comparisons; it is not proof that the outcomes have different underlying effects.

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 events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect under the planning assumptions, if that effect and the model assumptions were true. The 90% power column uses a higher target chance of detecting that effect and therefore generally calls for more participants per arm. These are design-planning quantities, not guarantees about the results of a future study.

The planning examples use the observed group contrast as their starting point, then consider smaller fractions of that effect. Smaller effects need more participants to detect with the same target power, because they are harder to distinguish from random variation. The figures are especially sensitive to the observed effect used as the starting point, so they should not be treated as a reliable reconstruction of the trial’s original sample-size planning.

This is not observed power. The trial’s original sample-size justification and design assumptions are not reported in the registry record. The listed calculations are planning illustrations based on the observed effect and the assumptions stated above, rather than an assessment of the probability that the completed trial detected a true effect.

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 = -3.400; pooled standard deviation σ = 1.051.
2. n = 2 × (1.96 + 0.842)² × 1.051² / -3.400² = 1.5, rounded up to 2 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 <- -3.4                      # observed difference in means
sigma <- 1.05118980208143                     # 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(232817)
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 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 50% of observed effect: n per arm = 7 (80% power), 9 (90% power)
power.t.test: 2.9 
Simulated power at n = 2 per arm: 0.429 (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 lists a primary pain-score outcome and one secondary outcome, cumulative morphine usage. It reports unadjusted p-values for the posted comparisons and does not report a multiplicity adjustment. When more than one outcome, time point, subgroup, or contrast is tested, repeated testing can increase the chance of at least one result appearing statistically unusual even if the underlying null hypotheses are true. In general, a prespecified hierarchy or adjustment can address that issue, but the registry record does not state whether one was planned or used.

The primary pain score combines observations from multiple postoperative assessment times into an average. Time-specific results are not posted. The record does not say whether the average was the sole prespecified primary analysis, whether time-specific comparisons were also planned, or whether any other outcomes or contrasts were examined. The absence of those details makes it difficult to assess the scope of testing or the role of the displayed unadjusted p-values.

Missing-data handling is not reported in the registry record. The record lists 23 enrolled participants and 10 participants in each posted primary outcome group, but it does not provide a participant-flow account explaining which enrolled participants contributed to each outcome or why others may not appear in the outcome groups. The number of missing pain ratings, if any, and the approach used to handle them are also not reported.

The analysis population is not defined in the registry record. It does not state whether the reported comparisons use all randomized participants, only participants with available outcome data, or another set. It also does not report an intention-to-treat or per-protocol analysis. These distinctions matter because the set of participants analyzed and the handling of missing outcomes can affect the estimated group contrast.

The registry does not report a detailed statistical analysis plan, covariate adjustments, interim analyses, or subgroup-analysis procedures. These should not be inferred from the posted outcome summary. Without those details, the reported comparisons can be described, but it is not possible to determine how fully they reflect a prespecified analysis strategy.

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.

The serious adverse event summary lists 10 participants at risk in each group. It reports 0 serious adverse events in the nicotine group and 0 in the placebo group, with 0 deaths in each group. The record also lists 10 participants at risk for other adverse events in each group and reports 0 other adverse events in either group. No serious adverse event terms are listed.

These figures describe the adverse events recorded in the registry for the listed groups. They do not establish that no adverse events occurred outside the reporting scope or that the groups have identical safety profiles. The registry record does not provide further detail about event definitions, collection procedures, follow-up completeness, severity grading, or causal assessment. With the small numbers of participants listed, the absence of recorded events should be interpreted as a limited observation rather than a precise estimate of event risk.

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

The primary result describes a lower average postoperative pain score in the posted nicotine group than in the placebo group. The reported difference is -3.4, and its 95% confidence interval is below zero. This is the principal quantitative finding in the registry’s posted primary comparison. It is an estimate for the groups and outcome as reported, not a statement about every participant or every postoperative assessment time.

The result does not, by itself, establish how the contrast varied between isoflurane and propofol anesthesia. Although the broader study question concerns those two anesthetic contexts, the posted outcome comparison is organized as nicotine versus placebo, without separate estimates by anesthesia. The record therefore does not show whether anesthetic type changed the nicotine-placebo contrast, nor does it provide a direct estimate of the difference between the anesthesia groups.

The result also does not establish the mechanism behind the observed contrast. The study summary describes interest in potential pronociceptive action of isoflurane, but the posted result does not test a reported interaction between anesthesia and nicotine. The registry does not report the detailed model, planned contrasts, or analysis plan needed to connect the overall comparison to that mechanistic question.

The secondary outcome, cumulative morphine usage, is less conclusive in its reported comparison: its confidence interval includes zero, and its unadjusted p-value is 0.148. This means the posted secondary evidence is uncertain, rather than establishing either a difference or no difference. The record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the outcomes.

Finally, the registry outcome groups each list 10 participants, while overall enrollment is 23. The record does not explain participant flow, missing data, or the analysis population. These limitations, together with the small reported groups and absent anesthesia-specific estimates, constrain how broadly the posted findings can be interpreted. They describe the recorded results without establishing the effects in other populations or settings.

17. Why This Trial Matters Statistically

This trial is statistically notable because its research question combines two factors: anesthetic context and intranasal nicotine or placebo. When a study is designed around more than one factor, the scientific question may concern both average group differences and whether the effect of one factor changes across levels of the other. The posted outcome comparison is nicotine versus placebo, but separate anesthesia-specific estimates and an interaction result are not reported. That distinction shows why the structure of the scientific question and the structure of the reported analysis must be examined together.

The primary endpoint also compresses repeated measurements into one average. This creates a concise summary of pain ratings over the postoperative period, but it cannot show whether group patterns differed at particular assessment times. The measurement strategy illustrates a general trade-off: summarizing repeated outcomes can simplify interpretation while removing information about timing and variation in the response pattern.

The contrast between the primary and secondary outcomes is another useful statistical lesson. The primary mean difference has a confidence interval below zero, whereas the secondary interval includes zero. Different outcomes can have different variability and precision, so a consistent-looking direction does not make every endpoint equally informative. Unadjusted testing across multiple outcomes also requires care, particularly when the registry does not describe a prespecified multiplicity strategy.

Finally, enrollment and outcome-group counts are not interchangeable. The record lists enrollment of 23 and outcome groups of 10 participants each, but does not explain participant flow or define the analysis population. Transparent reporting of these details is important for understanding which observations support an estimate and how missing outcomes were handled. The record gives useful numerical results, while leaving several design and analysis details unavailable.

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 principal limitation specific to interpreting this record is that the displayed primary comparison is by nicotine versus placebo, while the stated research question also concerns isoflurane versus propofol anesthesia. The posted results do not give separate outcome estimates by anesthesia group or a reported analysis of whether the nicotine-placebo contrast differs across anesthetics. This prevents direct evaluation of the anesthesia-specific question from the posted comparison.

The posted outcome groups list 10 participants each, while the enrollment field lists 23. The registry does not report participant flow, the reason for the difference, or the analysis population. It also does not state how missing pain scores or other missing outcome measurements were handled. These omissions limit assessment of potential selection or missing-data effects.

The primary pain outcome is an average across the listed assessment times. The registry does not post time-specific results, so the average cannot reveal whether the pattern differed during particular parts of the postoperative period. The record also does not report individual-level data, adjusted estimates, or model diagnostics.

The registry’s description of masking differs between fields: the masking classification is triple, while the brief summary calls the trial double-blinded. It does not explain who was masked or how masking was implemented. Detailed randomization procedures, the original sample-size justification, a statistical analysis plan, multiplicity procedures, and interim-analysis information are not reported in the registry record.

The trial is described as involving adult women undergoing uterine surgery, and the posted outcome groups are small. The record does not support conclusions about populations beyond those described. The safety summary also reports zero events in the listed groups but provides limited detail about event ascertainment and follow-up, so it should not be interpreted as a comprehensive safety assessment.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Anesthesia and Postoperative Pain — NCT00232817.
• Registry record last updated 2024-07-12; status last verified 2024-06.
• Results first posted 2024-07-12.
• 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 phase 4 randomized, parallel-group trial sponsored by Columbia University. Its broader question concerns postoperative pain in the context of isoflurane or propofol anesthesia and intranasal nicotine or placebo. The record lists enrollment of 23 and identifies adult women undergoing uterine surgery in the study summary.

The posted primary outcome is the average Numerical Rating Scale pain score up to 24 hours. The nicotine-placebo comparison reports a mean difference of -3.4, with a 95% confidence interval from -4.321 to -2.479 and an unadjusted p-value of <0.001. The one posted secondary outcome is cumulative morphine usage. Separate anesthesia-specific estimates, detailed participant flow, missing-data procedures, and the original analysis plan are not reported in the registry record.