Preventing Propofol-associated Injection Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preventing Propofol-associated Injection Pain (NCT00864682), a randomized phase 4 study. The primary outcome is Verbal Pain Score.

2. Clinical Question

3. Trial Design

The registry identifies NCT00864682 as a completed Phase 4, randomized, double-blind, parallel-group trial sponsored by Benaroya Research Institute. The recorded start was 2008-01, and primary completion was 2009-03. Enrollment was 156. The registry does not report the randomization procedure, the method used to maintain blinding, or the allocation ratio.

Three arms are described. The control arm received saline pretreatment and saline admixture. The lidocaine pretreatment arm received lidocaine pretreatment and a saline-propofol admixture. The lidocaine-propofol admixture arm received saline pretreatment and lidocaine mixed with propofol. The brief summary calls the study placebo-controlled and states the intended comparison between the two lidocaine approaches, with both expected to be superior to placebo.

The primary endpoint was assessed immediately after injection, at one time assessment. The posted primary-outcome arm counts are 50 for control, 50 for lidocaine-propofol admixture, and 51 for lidocaine pretreatment. These outcome counts do not equal the recorded enrollment; the registry record does not explain the difference or state how participants without posted primary scores were handled.

The planned sample-size justification, target allocation, eligibility criteria, full protocol, and prespecified analysis plan are not reported in the registry record. The registry also does not explain how allocation concealment, adherence, or deviations from assigned treatment were addressed. Those details cannot be inferred from the randomized and double-blind labels alone.

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 Verbal Pain Score, measured over Immediately after injection of study drug. One time assessment..

The primary endpoint is an 11-point verbal pain score, ranging from 0 for no pain to 10 for worst imaginable pain. Participants were assessed immediately after injection of the study drug. The registry reports the endpoint as a median with an inter-quartile range, a summary suited to describing the center and spread of observed scores without relying on a mean and standard deviation.

Pain is the direct experience the trial sought to compare across its injection approaches. The numeric scale turns a subjective report into an ordered outcome that can be summarized and statistically compared. Its interpretation remains tied to the scale: a score is a participant’s reported pain at the specified assessment, not a measure of pain at other times or of a broader clinical outcome.

The reported medians were 3 for control, 0 for lidocaine-propofol admixture, and 0 for lidocaine pretreatment. The respective inter-quartile ranges were 0 to 6, 0 to 2, and 0 to 0. These summaries describe the observed distributions in the posted analysis groups. The registry does not report a primary-outcome confidence interval, a pairwise treatment effect, or a threshold defining a clinically important score difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the overall primary test assess?

The registry reports a Kruskal-Wallis test across the control, lidocaine-propofol admixture, and lidocaine pretreatment groups, with p < 0.001. As a general statistical explanation, the Kruskal-Wallis procedure compares the rank distributions of independent groups. It is often used for ordered outcomes when a comparison based on ranks is appropriate. It is not simply a test of medians in every possible distributional setting: differences in spread or broader distributional shape can also contribute to a result. The posted medians and inter-quartile ranges provide useful descriptions, while the overall test supplies evidence about a difference across groups.

A p-value is a measure of how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of a difference. The reported p-value is for the overall comparison. The registry does not report the test statistic, degrees of freedom, assumptions checks, or post-test comparisons.

Why use medians and inter-quartile ranges?

A median gives the midpoint of an ordered set of observations, and the inter-quartile range describes the central half of those observations. As a general statistical explanation, these summaries can be informative when an outcome is ordinal, bounded, or concentrated at a scale endpoint. Here, the endpoint is a bounded verbal pain scale, and the reported distributions include a median of zero in both lidocaine arms. A mean would answer a different descriptive question and could be more sensitive to the upper tail. The registry reports medians and inter-quartile ranges, not means or standard deviations.

The summaries do not reveal the full distributions. Scores can differ in ways not captured by a median and inter-quartile range, and a floor value of zero can create clustering. The posted data do not include score frequencies, individual observations, or a detailed description of handling of ties. The registry record also does not report a rationale for selecting the Kruskal-Wallis test.

How should the secondary comparisons be read?

The registry reports a Chi-squared test across the three groups for complete alleviation of injection pain, with p <0.008. This is another overall test, applied to a binary outcome, and does not by itself provide a pairwise estimate. The posted counts are 14 of 50 in control, 28 of 50 in the admixture arm, and 40 of 51 in the pretreatment arm.

For interpretation, unadjusted pairwise recalculations compare each active arm with control. The recalculated risk difference is 0.28 for admixture versus control, with a 95% confidence interval of 0.095 to 0.466 and an unadjusted p-value of 0.005. For pretreatment versus control, the recalculated risk difference is 0.504 at three decimal places, with a 95% confidence interval of 0.336 to 0.672 and an unadjusted p-value of <0.001. The registry’s reported overall Chi-squared p-value and these recalculated pairwise results answer related but distinct questions.

A risk difference expresses the difference between the observed proportions in two groups. A confidence interval conveys the range of values compatible with the data and the calculation method, subject to its assumptions. As a general statistical explanation, a narrow interval indicates greater precision than a wide interval, while an interval that includes zero is compatible with no risk difference under the corresponding confidence procedure. These simple recalculations are not adjusted for other endpoints or comparisons and should not be mistaken for the sponsor’s full analysis.

The recalculations also include relative measures: the risk ratio is 2.0 for admixture versus control and 2.801 for pretreatment versus control; the odds ratios are 3.273 and 9.351, respectively. These measures describe the binary complete-alleviation outcome and do not replace the absolute risk differences. Their numerical magnitudes depend on the measure used, so the measure and its uncertainty should be considered together rather than treating one as a universal summary.

What do the planning illustrations mean?

The planning illustrations use the observed complete-alleviation effects and assume two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. For planning for 100% of the observed admixture effect, the illustration gives 48 participants per arm for 80% power and 64 participants per arm for 90% power. For 75% of that observed effect, the corresponding figures are 84 and 111 participants per arm; for 50%, they are 182 and 242.

For planning for 100% of the observed pretreatment effect, the illustration gives 15 participants per arm for 80% power and 19 participants per arm for 90% power. For 75% of that effect, the figures are 27 and 35 participants per arm; for 50%, they are 59 and 78. These are planning illustrations based on observed effects, not observed power and not the trial’s reported design justification. The registry does not report the trial’s own sample-size assumptions or calculations. Because observed effects can be imprecise, these illustrations should not be read as definitive design requirements.

10. Analyses Reported by the Sponsor

The sponsor’s posted primary analysis is an overall Kruskal-Wallis test across the three arms, reported as p < 0.001. The sponsor’s posted secondary analysis is an overall Chi-squared test across the three arms for complete alleviation of injection pain, reported as p <0.008. Those are the registry’s reported analyses and remain distinct from the simple pairwise recalculations of the secondary counts.

The recalculated secondary risk differences, confidence intervals, risk ratios, odds ratios, and unadjusted p-values use posted arm counts to compare each lidocaine approach with control. They are not a reproduction of every detail of the sponsor’s analysis, and they do not replace the sponsor’s overall tests. The primary endpoint has no posted recalculated pairwise estimates in the registry record, so the overall primary p-value should not be presented as if it were a pairwise effect estimate.

No discrepancy is indicated between the posted summaries and the recalculations. Even so, the analyses answer different questions: the sponsor’s reported tests evaluate an overall group difference, while the simple recalculations focus on two secondary pairwise contrasts. The registry does not report the full statistical analysis plan or enough detail to establish whether the sponsor used additional methods beyond the posted tests.

11. Multiplicity, Missing Data and Analysis Populations

The registry names complete alleviation of injection pain and satisfaction with anesthetic technique as secondary outcomes, in addition to the primary verbal pain score. Complete-alleviation results are posted, but satisfaction results are not reported in the registry record. The sponsor reports an overall test for each posted endpoint, while the simple recalculations include two pairwise secondary comparisons against control.

When multiple outcomes or comparisons are examined, unadjusted significance tests can overstate the strength of evidence if treated as though only a single test had been planned. As a general statistical explanation, a multiplicity strategy may define which tests are confirmatory and how error rates are controlled. The registry record does not report whether there was a prespecified hierarchy, a correction for multiple testing, or a distinction between confirmatory and exploratory analyses. The unadjusted recalculated p-values should therefore be interpreted with caution and are not evidence that multiplicity was controlled.

Missing-data handling and analysis populations are also not reported in the registry record. Enrollment was 156, while primary-outcome counts are 50, 50, and 51 across the arms. Safety denominators are different again. The record does not explain these differences, state whether all randomized participants were included in each analysis, describe exclusions, or give reasons for absent measurements. It also does not specify whether an intention-to-treat population, a per-protocol population, or another population was used.

The registry does not report how missing scores were handled, whether any imputation was used, or whether sensitivity analyses were conducted. These omissions matter because the interpretation of a randomized comparison can depend on which participants contribute to each outcome and how incomplete observations are treated. The posted results can describe the analyzed counts, but cannot establish the assumptions or procedures behind those counts.

The full statistical analysis plan, sample-size justification, interim analyses, and prespecified multiplicity methods are not reported in the registry record. No assumptions about those procedures should be inferred from the reported p-values or trial design labels.

12. 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 reports zero serious adverse events in each safety group: 0 of 52 in control, 0 of 51 in the lidocaine-propofol admixture arm, and 0 of 53 in the lidocaine pretreatment arm. It also reports zero other adverse events in those same respective at-risk groups. These are the posted counts for the registry’s safety categories.

Zero reported events in these groups means that no events were recorded in the posted results for the stated denominators. It does not establish that the risk of an event is absent, nor does it show how frequently events might occur outside this trial. The registry gives no serious adverse event terms, and the death counts are not reported in the registry record.

Safety denominators differ from the primary-outcome arm counts. The registry does not explain the difference, describe the observation period for adverse events, or provide details about event collection and coding. The figures should therefore be read as reported counts, not as a comprehensive account of safety or a comparison adjusted for differences in follow-up or exposure.

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

The posted primary summaries show lower median verbal pain scores in both lidocaine groups than in the saline control group, alongside an overall Kruskal-Wallis result of p < 0.001. The secondary complete-alleviation counts follow a direction consistent with those primary summaries, and the registry reports an overall Chi-squared result of p <0.008. Together, these results describe the observed pattern in the posted data.

They do not provide a complete estimate of the size and precision of every primary comparison. The primary result is an overall test rather than a set of pairwise estimates, and the registry does not report a primary confidence interval. The secondary pairwise estimates are simple unadjusted recalculations, not substitutes for a prespecified analysis. The satisfaction outcome has no posted results.

Statistical evidence of differences does not by itself establish clinical importance. The registry does not report a threshold for a clinically important change in the verbal pain scale, participant-level score distributions, or detailed contextual information about how the outcome was assessed. The medians and inter-quartile ranges describe the middle of the observed scores, not each individual’s experience.

These data also do not establish that either approach is preferable for a particular person or setting. The registry record does not provide the detailed eligibility criteria, full analysis plan, missing-data procedures, or comprehensive safety information needed to answer broader questions. The results are best understood as findings from the recorded groups and outcomes, with those reporting limitations kept in view.

14. Why This Trial Matters Statistically

This trial raises a useful statistical problem: how to compare an ordered, bounded patient-reported score across randomized groups when values cluster at the low end of the scale. Reporting medians and inter-quartile ranges makes the central distribution visible without implying that a mean-based model was used. The Kruskal-Wallis test supplies an overall comparison, but it does not by itself identify the pairwise contrasts or quantify their size.

The trial also illustrates why endpoint definitions matter. The verbal pain score retains ordered information across the scale, whereas complete alleviation reduces the experience to whether pain was absent. Those outcomes can point in a similar direction while answering different questions. Statistical summaries should remain linked to the outcome that was actually measured.

Another important issue is the distinction between an omnibus test and pairwise comparisons. The registry’s reported p-values concern overall differences across the arms. The recalculated secondary contrasts focus on each active arm versus control and are unadjusted. Treating the two kinds of results as interchangeable would obscure both the test question and the uncertainty around an effect estimate.

Finally, the record shows why completeness of reporting affects interpretation. The posted outcome counts, enrollment, and safety denominators do not align, and the registry does not explain the analysis populations or missing-data handling. The sample-size illustrations are based on observed secondary effects rather than a reported design calculation. These features do not erase the posted results, but they define what can be concluded from them and what remains uncertain.

15. 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 registry record gives a brief trial description and summary results, but not the full protocol or statistical analysis plan. Specific eligibility criteria, participant characteristics, randomization details, allocation concealment, and the procedures used to maintain blinding are not reported in the registry record. The randomized and double-blind labels do not answer those methodological questions.

The posted primary endpoint is summarized by medians and inter-quartile ranges, with an overall p-value. The registry does not report pairwise primary-outcome estimates, confidence intervals, the test statistic, or score-level data. It is therefore not possible to quantify the primary differences and their precision from the reported test alone. The record also does not define a clinically important difference on the pain scale.

Enrollment is 156, while the posted primary-outcome groups contain 50, 50, and 51 participants. Safety groups use denominators of 52, 51, and 53. The registry does not explain the distinct counts or describe missing observations, exclusions, or analysis populations. Without that information, the relationship between enrollment and each posted analysis cannot be established.

The secondary satisfaction outcome is named but its results are not reported in the registry record. Complete-alleviation pairwise measures are simple unadjusted recalculations, and the registry does not state whether multiplicity was addressed. The reported overall test and recalculated contrasts must be interpreted as distinct analyses. The sample-size illustrations use observed effects and are not the trial’s own design justification.

Safety reporting is limited to the posted at-risk denominators and zero event counts. Event definitions, collection duration, and detailed safety methods are not reported in the registry record; death counts are also not reported. These limitations constrain what can be concluded about outcome completeness, the precision of treatment comparisons, and the breadth of safety evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preventing Propofol-associated Injection Pain — NCT00864682.
• Registry record last updated 2021-01-27; status last verified 2021-01.
• Results first posted 2009-08-03.
• 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.

19. Record Summary

NCT00864682 was a completed, randomized, double-blind, parallel-group Phase 4 trial sponsored by Benaroya Research Institute, with enrollment of 156. It compared saline control, lidocaine mixed with propofol, and lidocaine pretreatment followed by a saline-propofol admixture. Primary completion was 2009-03.

The primary outcome was an 11-point verbal pain score assessed immediately after injection. Reported medians were 3 for control and 0 for each lidocaine arm; the overall Kruskal-Wallis result was p < 0.001. Complete alleviation of injection pain was the secondary outcome with posted results, and the registry reported an overall Chi-squared result of p <0.008. Satisfaction results are not reported in the registry record.

The posted findings describe lower pain scores in the lidocaine groups than in control, but the record lacks primary pairwise estimates and key details about analysis populations, missing data, and multiplicity. Safety counts report zero serious and zero other adverse events in each listed at-risk group.